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pmid:31804459

SKA3 Promotes tumor growth by regulating CDK2/P53 phosphorylation in hepatocellular carcinoma.

Yuchen Hou · Ziming Wang · Shanzhou Huang · Chengjun Sun · Jingya Zhao · Jiayu Shi · Zhongqiu Li · Zekang Wang · Xiaoshun He · Nga Lei Tam · Linwei Wu

Cell death & disease · 2019 doi:10.1038/s41419-019-2163-3

Paper

complete

Experiment

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Data

partial

Analysis

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pmid:31804459
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title
SKA3 Promotes tumor growth by regulating CDK2/P53 phosphorylation in hepatocellular carcinoma.
doi
10.1038/s41419-019-2163-3
pmid
31804459
authors array · 11 items
[0]
Yuchen Hou
[1]
Ziming Wang
[2]
Shanzhou Huang
[3]
Chengjun Sun
[4]
Jingya Zhao
[5]
Jiayu Shi
[6]
Zhongqiu Li
[7]
Zekang Wang
[8]
Xiaoshun He
[9]
Nga Lei Tam
[10]
Linwei Wu
journal
Cell death & disease
year
2019
abstract
Spindle and kinetochore-related complex subunit 3 (SKA3) is a component of the spindle and kinetochore-related complexes and is essential for accurate timing of late mitosis. However, the relationship between SKA3 and hepatocellular carcinoma (HCC) has not yet been fully elucidated. Gene expression omnibus (GEO) (GSE62232, GSE45436, GSE6764, and GSE36376) and The Cancer Atlas (TCGA) datasets were analyzed to identify differential expression genes. Cell proliferation ability was analyzed using Cell Counting Kit-8 (CCK8) assay and plate clone formation assay, while scratch wound healing assay and transwell assay were used to analyze cell invasion. The role of SKA3 in vivo was explored using subcutaneous xenotransplantation model and lung metastasis model. Bioinformatics analysis found that hepatocellular carcinoma patients with high levels of expression of SKA3 have a poor prognosis. Similarly, immunohistochemical staining of 236 samples of tumors also found higher SKA3 expression in them, than in adjacent normal liver tissues. Significant levels of inhibition of in vivo and in vitro tumor proliferation and invasion result from the downregulation of SKA3. Mechanistically, SKA3 was found to affect tumor progression through the cell cycle and P53 signaling pathway as shown by the gene enrichment analysis (GSEA). G2/M phase arrest and severe apoptosis was also found to result from SKA3 knockdown, as shown by the inhibition of CDK2/p53 phosphorylation together with downregulation of BAX/Bcl-2 expression in HCC cells. Overall, these findings uncover the role of SKA3 in regulating the apoptosis and proliferation of hepatocellular carcinoma cells. This study was able to uncover new information on the tumorigenesis mechanism in hepatocellular carcinoma.
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We acquired HCC expression data from GEO (datasets GSE62232, GSE45436, GSE36376, and GSE6764; http://www.ncbi.nlm.nih.gov/geo) and TCGA (http://gdc.cancer.gov/) databases. Log2 conversion was performed for all data in data standardization. EdgeR package was used to analyse gene differential expression for the data in count form. Limma package was used for the data in GEO database. We selected genes whose |logFC (fold change)| > 1 and p-value < 0.05 as differential expression genes.
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We acquired HCC expression data from GEO (datasets GSE62232, GSE45436, GSE36376, and GSE6764; http://www.ncbi.nlm.nih.gov/geo) and TCGA (http://gdc.cancer.gov/) databases. Log2 conversion was performed for all data in data standardization. EdgeR package was used to analyse gene differential expression for the data in count form. Limma package was used for the data in GEO database. We selected genes whose |logFC (fold change)| > 1 and p-value < 0.05 as differential expression genes.
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The datasets used and/or analyzed during the current study can be obtained from the corresponding author on reasonable request.
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Gene Expression Profiles of both tumor and adjacent non-tumor liver Identify Hepatocellular Carcinoma Patients at High Risk of Recurrence after Curative Hepatectomy
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[133]
GSM1104199
sample_count
134
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null
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null
platform
570
taxon
Homo sapiens
title
Gene expression profiles of human hepatocellular carcinoma
resolution_checked_at
2026-11-01T15:39:54Z
resolution_check
identifier_resolution_only_no_download_no_licence_read
downloaded
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licence_read
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[3] object · 15 fields
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data:geo:GSE62232
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structure object · 15 fields
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GEO accession URL
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access_statement_kind
data_availability_statement
sample_accessions array · 91 items
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GSM1523392
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GSM1523394
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[67]
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GSM1523399
[71]
GSM1523400
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GSM1523401
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GSM1523403
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GSM1523404
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GSM1523405
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GSM1523406
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GSM1523407
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GSM1523408
[80]
GSM1523409
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GSM1523410
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GSM1523411
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GSM1523412
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GSM1523415
[87]
GSM1523416
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GSM1523417
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GSM1523418
[90]
GSM1523419
sample_count
91
group_sizes
null
group_sizes_basis
null
platform
570
taxon
Homo sapiens
title
Large-scale gene expression profiling of 81 hepatocellular carcinomas
resolution_checked_at
2026-11-01T15:39:55Z
resolution_check
identifier_resolution_only_no_download_no_licence_read
downloaded
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licence_read
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[4] object · 15 fields
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data:geo:GSE6764
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null
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The datasets used and/or analyzed during the current study can be obtained from the corresponding author on reasonable request.
structure object · 15 fields
repository
GEO
access_route
GEO accession URL
access_statement_verbatim
The datasets used and/or analyzed during the current study can be obtained from the corresponding author on reasonable request.
access_statement_kind
data_availability_statement
sample_accessions array · 75 items
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GSM155920
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GSM155988
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GSM155991
[73]
GSM155992
[74]
GSM155993
sample_count
75
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null
group_sizes_basis
null
platform
570
taxon
Homo sapiens
title
Genome-wide molecular profiles of HCV-induced dysplasia and hepatocellular carcinoma
resolution_checked_at
2026-11-01T15:39:55Z
resolution_check
identifier_resolution_only_no_download_no_licence_read
downloaded
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[5] object · 16 fields
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asset:table:pmid:31804459:1
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jats-table
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Correlation between SKA3 expressions with clinic-pathological characteristics of HCC.
structure object · 5 fields
pmcid
PMC6895034
section_index
3
section_title
Clinical patient specimens and information
row_count
32
column_count
5
table object · 8 fields
label
Table 1
caption
Correlation between SKA3 expressions with clinic-pathological characteristics of HCC.
rows array · 32 items
[0] array · 4 items
[0]
Clinicopathological Variables
[1]
N
[2]
SKA3 expression
[3]
P-Value
[1] array · 2 items
[0]
Low (102)
[1]
High (134)
[2] array · 5 items
[0]
Sex
[1]
[2]
[3]
[4]
0.244
[3] array · 5 items
[0]
Male
[1]
120
[2]
55
[3]
65
[4]
[4] array · 5 items
[0]
Female
[1]
116
[2]
47
[3]
69
[4]
[5] array · 5 items
[0]
Age, years
[1]
[2]
[3]
[4]
0.438
[6] array · 5 items
[0]
<50
[1]
139
[2]
59
[3]
80
[4]
[7] array · 5 items
[0]
≥50
[1]
97
[2]
43
[3]
54
[4]
[8] array · 5 items
[0]
AFP, ng/L
[1]
[2]
[3]
[4]
8.856e−11
[9] array · 5 items
[0]
<200
[1]
153
[2]
89
[3]
64
[4]
[10] array · 5 items
[0]
≥200
[1]
83
[2]
13
[3]
70
[4]
[11] array · 5 items
[0]
HBsAg
[1]
[2]
[3]
[4]
0.398
[12] array · 5 items
[0]
Negative
[1]
82
[2]
34
[3]
48
[4]
[13] array · 5 items
[0]
Positive
[1]
154
[2]
68
[3]
86
[4]
[14] array · 5 items
[0]
Tumor size, cm
[1]
[2]
[3]
[4]
3.29e–11
[15] array · 5 items
[0]
≤5
[1]
138
[2]
84
[3]
54
[4]
[16] array · 5 items
[0]
>5
[1]
98
[2]
18
[3]
80
[4]
[17] array · 5 items
[0]
Tumor nodule number
[1]
[2]
[3]
[4]
8.29e−07
[18] array · 5 items
[0]
Solitary
[1]
146
[2]
81
[3]
65
[4]
[19] array · 5 items
[0]
Multiple (≥2)
[1]
90
[2]
21
[3]
69
[4]
[20] array · 5 items
[0]
Cancer embolus
[1]
[2]
[3]
[4]
5.83e−14
[21] array · 5 items
[0]
Absence
[1]
152
[2]
92
[3]
60
[4]
[22] array · 5 items
[0]
Presence
[1]
84
[2]
10
[3]
74
[4]
[23] array · 5 items
[0]
TNM stage
[1]
[2]
[3]
[4]
1.6e−05
[24] array · 5 items
[0]
Early (I & II)
[1]
157
[2]
83
[3]
74
[4]
[25] array · 5 items
[0]
Late (III & IV)
[1]
79
[2]
19
[3]
60
[4]
[26] array · 5 items
[0]
Differentiation grade
[1]
[2]
[3]
[4]
0.002
[27] array · 5 items
[0]
Well
[1]
173
[2]
85
[3]
88
[4]
[28] array · 5 items
[0]
Poor
[1]
63
[2]
17
[3]
46
[4]
[29] array · 5 items
[0]
P53 expression
[1]
[2]
[3]
[4]
0.021
[30] array · 5 items
[0]
High
[1]
95
[2]
33
[3]
62
[4]
[31] array · 5 items
[0]
Low
[1]
141
[2]
69
[3]
72
[4]
locator
section[3]/table-wrap[1]#Tab1
[6] object · 16 fields
id
asset:table:pmid:31804459:2
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table
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jats-table
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application/vnd.jats.table+json
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null
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sha256:0afa91a3ec149fd18d1d864d734b8ee24212e7d803e2954b2961552b8f661c39
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read_table
reader_status
available
identifier
section[26]/table-wrap[1]#Tab2
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null
note
Univariate and multivariate Cox regression analysis of risk factors associated with overall survival.
structure object · 5 fields
pmcid
PMC6895034
section_index
26
section_title
Overexpression of SKA3 in HCC patients predicts poor survival
row_count
12
column_count
7
table object · 8 fields
label
Table 2
caption
Univariate and multivariate Cox regression analysis of risk factors associated with overall survival.
rows array · 12 items
[0] array · 3 items
[0]
Variables
[1]
Univariate analysis
[2]
Multivariate analysis
[1] array · 6 items
[0]
HR
[1]
95% CI
[2]
P-Value
[3]
HR
[4]
95% CI
[5]
P-Value
[2] array · 7 items
[0]
SKA3 expression (high vs. low)
[1]
2.239
[2]
1.574–3.187
[3]
7.59e−06
[4]
1.299
[5]
0.829–2.034
[6]
0.25
[3] array · 7 items
[0]
Sex (male vs. female)
[1]
0.935
[2]
0.67–1.305
[3]
0.69
[4]
[5]
[6]
[4] array · 7 items
[0]
Age (≥50 vs. <50)
[1]
0.899
[2]
0.659–1.226
[3]
0.50
[4]
[5]
[6]
[5] array · 7 items
[0]
HBsAg (positive vs. negative)
[1]
0.944
[2]
0.671–1.329
[3]
0.74
[4]
[5]
[6]
[6] array · 7 items
[0]
AFP (≥200 ng/ml vs. <200 ng/ml)
[1]
1.797
[2]
1.279–2.525
[3]
7.31e−04
[4]
1.048
[5]
0.692–1.586
[6]
0.83
[7] array · 7 items
[0]
Tumor size (>5 cm vs. ≤5 cm)
[1]
2.441
[2]
1.742–3.421
[3]
2.19e−07
[4]
1.688
[5]
1.136–2.509
[6]
0.0095
[8] array · 7 items
[0]
Tumor nodule number (multiple vs. single)
[1]
1.797
[2]
1.284–2.514
[3]
6.27e−04
[4]
1.086
[5]
0.744–1.585
[6]
0.67
[9] array · 7 items
[0]
Cancer embolus (presence vs. absence)
[1]
2.875
[2]
2.035–4.061
[3]
2.07e−09
[4]
1.878
[5]
1.231–2.866
[6]
0.0035
[10] array · 7 items
[0]
TNM stage (late vs. early)
[1]
2.095
[2]
1.485–2.956
[3]
2.5e−05
[4]
1.209
[5]
0.804–1.818
[6]
0.36
[11] array · 7 items
[0]
Differentiation grade (poor vs. well)
[1]
1.545
[2]
1.08–2.211
[3]
0.017
[4]
0.970
[5]
0.648–1.452
[6]
0.88
locator
section[26]/table-wrap[1]#Tab2
[7] object · 16 fields
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asset:table:pmid:31804459:3
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table
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jats-table
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application/vnd.jats.table+json
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null
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sha256:f84668530aca17eb0cb22a5431bf986381a66a472dc6915f59328b4eb0e643df
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access
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read_table
reader_status
available
identifier
section[26]/table-wrap[2]#Tab3
version
null
note
Univariate and multivariate Cox regression analysis of risk factors associated with disease-free survival.
structure object · 5 fields
pmcid
PMC6895034
section_index
26
section_title
Overexpression of SKA3 in HCC patients predicts poor survival
row_count
12
column_count
7
table object · 8 fields
label
Table 3
caption
Univariate and multivariate Cox regression analysis of risk factors associated with disease-free survival.
rows array · 12 items
[0] array · 3 items
[0]
Variables
[1]
Univariate analysis
[2]
Multivariate analysis
[1] array · 6 items
[0]
HR
[1]
95% CI
[2]
P-Value
[3]
HR
[4]
95% CI
[5]
P-Value
[2] array · 7 items
[0]
SKA3expression (high vs. low)
[1]
2.107
[2]
1.54–2.883
[3]
3.18e−06
[4]
1.501
[5]
1.017–2.216
[6]
0.04
[3] array · 7 items
[0]
Sex (male vs. female)
[1]
1.107
[2]
0.818–1.498
[3]
0.51
[4]
[5]
[6]
[4] array · 7 items
[0]
Age (≥50 vs. <50)
[1]
0.912
[2]
0.67–1.24
[3]
0.56
[4]
[5]
[6]
[5] array · 7 items
[0]
HBsAg (positive vs. negative)
[1]
1.441
[2]
1.04–1.998
[3]
0.028
[4]
1.745
[5]
1.234–2.466
[6]
0.0016
[6] array · 7 items
[0]
AFP (≥200 ng/ml vs. <200 ng/ml)
[1]
1.623
[2]
1.184–2.225
[3]
2.63e−03
[4]
1.042
[5]
0.707–1.536
[6]
0.83
[7] array · 7 items
[0]
Tumor size (>5 cm vs. ≤5 cm)
[1]
2.098
[2]
1.549–2.84
[3]
1.66e−06
[4]
1.667
[5]
1.174–2.365
[6]
0.0042
[8] array · 7 items
[0]
Tumor nodule number (multiple vs. single)
[1]
1.517
[2]
1.114–2.066
[3]
8.13e−03
[4]
1.077
[5]
0.76–1.525
[6]
0.68
[9] array · 7 items
[0]
Cancer embolus (presence vs. absence)
[1]
2.420
[2]
1.766–3.316
[3]
3.88e−08
[4]
2.002
[5]
1.046–3.832
[6]
0.0362
[10] array · 7 items
[0]
TNM stage (late vs. early)
[1]
1.451
[2]
1.049–2.008
[3]
0.025
[4]
1.051
[5]
0.715–1.547
[6]
0.80
[11] array · 7 items
[0]
Differentiation grade (poor vs. well)
[1]
1.480
[2]
1.064–2.058
[3]
0.02
[4]
0.909
[5]
0.62–1.333
[6]
0.62
locator
section[26]/table-wrap[2]#Tab3
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[4]
asset:data:geo:GSE62232 not downloaded
[5]
asset:data:geo:GSE62232 licence not read
[6]
asset:data:geo:GSE6764 not downloaded
[7]
asset:data:geo:GSE6764 licence not read
analysis object · 4 fields
state
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method-1
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differential_expression
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normalise_counts
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differential_expression_fit
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fdr_bh
missing_operations array · 0 items
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log2fc_threshold
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data_shapes array · 1 item
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count_matrix_with_condition
evidence object · 3 fields
score
1
band
verbatim
quote
We acquired HCC expression data from GEO (datasets GSE62232, GSE45436, GSE36376, and GSE6764; http://www.ncbi.nlm.nih.gov/geo) and TCGA (http://gdc.cancer.gov/) databases. Log2 conversion was performed for all data in data standardization. EdgeR package was used to analyse gene differential expression for the data in count form. Limma package was used for the data in GEO database. We selected genes whose |logFC (fold change)| > 1 and p-value < 0.05 as differential expression genes.
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method-2
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survival_analysis
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cox_proportional_hazards
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Survival analysis
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[0]
cox_ph
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parameters object · 0 fields
data_shapes array · 1 item
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time_to_event_with_censoring
evidence object · 3 fields
score
0.8
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Cox proportional hazards
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method-3
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differential_expression
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limma_voom
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Differential expression analysis
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normalise_counts
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differential_expression_fit
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fdr_bh
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count_matrix_with_condition
evidence object · 3 fields
score
0.8
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high
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Limma
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id
method-4
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correlation_analysis
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pearson
label
Correlation analysis
dsl_operations array · 1 item
[0]
pearson_r
missing_operations array · 0 items
parameters object · 0 fields
data_shapes array · 1 item
[0]
paired_numeric_columns
evidence object · 3 fields
score
0.8
band
high
quote
Pearson correlation
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gaps array · 1 item
[0]
method.reader_differs_from_extractor
capability object · 3 fields
state
complete
requirements array · 1 item
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capability_id
capability:computational_analysis
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assay_families array · 9 items
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meta_analysis
[1]
machine_learning
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survival_analysis
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statistical_regression
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pca
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molecular_docking
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network_analysis
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differential_expression
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gwas
candidate
Automated Assays Laravel application and simulated adapters
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readiness object · 8 fields
state
complete
tier
R1
blocked_on
nothing:replicable_now
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required_operations array · 3 items
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normalise_counts
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differential_expression_fit
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fdr_bh
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basis
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capability object · 4 fields
tier
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capability_id
capability:computational_analysis
availability_state
owned
basis
The computational analysis is owned. The physical bench the paper used is not, so a physical validation cannot be run here.
data object · 6 fields
tier
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accessions array · 4 items
[0]
GSE62232
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GSE45436
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GSE36376
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GSE6764
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[0]
GSE62232
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GSE45436
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GSE36376
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GSE6764
statements array · 1 item
[0]
The datasets used and/or analyzed during the current study can be obtained from the corresponding author on reasonable request.
basis
The paper names GSE62232, GSE45436, GSE36376, GSE6764 in Gene Expression Omnibus (GEO) and the accession resolves in the repository. No dataset was downloaded and no licence was read.
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normalise_counts
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fdr_bh
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source:pmid:31804459
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asset:table:pmid:31804459:2
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run_analysis
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data:geo:GSE36376
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review object · 5 fields
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extraction_review
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MiniMax-M3.1-Flash
provider
minimax
provider_family
minimax
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2026-10-31T18:17:12Z
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method
verbatim
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usage object · 3 fields
prompt_tokens
33212
completion_tokens
1530
cached_tokens
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[0] object · 4 fields
id
extraction
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review.independent_reader
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review.machine_critique
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review.human_critique
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execution.not_run
provenance object · 7 fields
entities array · 3 items
[0] object · 3 fields
id
pmid:31804459
type
paper
label
pmid:31804459
[1] object · 3 fields
id
source:pmid:31804459
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manuscript
label
PMID 31804459 full text
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data:geo:GSE36376
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dataset
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GEO GSE36376
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activity-reading-sci-2026-11-01
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classification
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pmid:31804459
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paper
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pmid:31804459
[1] object · 3 fields
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source:pmid:31804459
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manuscript
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PMID 31804459 full text
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data:geo:GSE36376
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dataset
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GEO GSE36376
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agent:corpus-assay-engine
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activity-read-31804459
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used array · 1 item
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source:pmid:31804459
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agent:minimax-reader
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used array · 1 item
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agent:corpus-assay-engine
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dsl_catalogue_fingerprint
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lineage object · 4 fields
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data_generation
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apoptosis_assay
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99e1195c7d6f
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99e1195c7d6f
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evidence array · 3 items
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nalysis (GSEA). G2/M phase arrest and severe apoptosis was also found to result from SKA3 knockdown
[1]
s uncover the role of SKA3 in regulating the apoptosis and proliferation of hepatocellular carcinom
[2]
lity was analyzed using Cell Counting Kit-8 (CCK8) assay and plate clone formation assay, whil
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assay:1
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99e1195c7d6f
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d to analyze cell invasion. The role of SKA3 in vivo was explored using subcutaneous xenotranspla
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tissues. Significant levels of inhibition of in vivo and in vitro tumor proliferation and invasio
[2]
used to measure the mice, and at week 8 the mice were sacrificed. Thereafter, in order to analyze the presenc
[3]
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on of SKA3 have a poor prognosis. Similarly, immunohistochemical staining of 236 samples of tumors also found
[1]
ographed and preserved. Ki-67 antibodies for immunohistochemistry staining was obtained from Bioss (bs-2130R).
[2]
SKA3 in HCC patients predicts poor survival Immunohistochemical results showed that 134 out of 236 HCC patie
[3]
clinical patients (Fig. 1j, k). We then used immunohistochemical staining to explore the status of P53 in tho
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apoptosis was also found to result from SKA3 knockdown, as shown by the inhibition of CDK2/p53 phos
[1]
boxplots and scatter plots. Cell culture and transfection Human hepatocellular carcinoma cell lines (L
[2]
order to inhibit the expression of SKA3, we transfected three small interfering RNAs (siRNAs) target
[3]
was mixed with pPACKH1 packaging plasmid and transfected into 293TN cells with sh-SKA3/NC. 3 days lat
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evidence array · 1 item
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We acquired HCC expression data from GEO (datasets GSE62232, GSE45436, GSE36376, and GSE6764; http://www.ncbi.nlm.nih.gov/geo) and TCGA (http://gdc.cancer.gov/) databases. Log2 conversion was performed for all data in data standardization. EdgeR package was used to analyse gene differential expression for the data in count form. Limma package was used for the data in GEO database. We selected genes whose |logFC (fold change)| > 1 and p-value < 0.05 as differential expression genes.
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Complete file
{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:31804459", "kind": "science-record", "revision": 8, "content_hash": "sha256:8b2015795e2d521cf7a17814b00ed195c589be5363afc600292b02cadac900e3", "created_at": "2026-11-01T15:40:53Z", "updated_at": "2026-11-01T22:44:23Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "SKA3 Promotes tumor growth by regulating CDK2/P53 phosphorylation in hepatocellular carcinoma.", "doi": "10.1038/s41419-019-2163-3", "pmid": "31804459", "authors": ["Yuchen Hou", "Ziming Wang", "Shanzhou Huang", "Chengjun Sun", "Jingya Zhao", "Jiayu Shi", "Zhongqiu Li", "Zekang Wang", "Xiaoshun He", "Nga Lei Tam", "Linwei Wu"], "journal": "Cell death & disease", "year": 2019, "abstract": "Spindle and kinetochore-related complex subunit 3 (SKA3) is a component of the spindle and kinetochore-related complexes and is essential for accurate timing of late mitosis. However, the relationship between SKA3 and hepatocellular carcinoma (HCC) has not yet been fully elucidated. Gene expression omnibus (GEO) (GSE62232, GSE45436, GSE6764, and GSE36376) and The Cancer Atlas (TCGA) datasets were analyzed to identify differential expression genes. Cell proliferation ability was analyzed using Cell Counting Kit-8 (CCK8) assay and plate clone formation assay, while scratch wound healing assay and transwell assay were used to analyze cell invasion. The role of SKA3 in vivo was explored using subcutaneous xenotransplantation model and lung metastasis model. Bioinformatics analysis found that hepatocellular carcinoma patients with high levels of expression of SKA3 have a poor prognosis. Similarly, immunohistochemical staining of 236 samples of tumors also found higher SKA3 expression in them, than in adjacent normal liver tissues. Significant levels of inhibition of in vivo and in vitro tumor proliferation and invasion result from the downregulation of SKA3. Mechanistically, SKA3 was found to affect tumor progression through the cell cycle and P53 signaling pathway as shown by the gene enrichment analysis (GSEA). G2/M phase arrest and severe apoptosis was also found to result from SKA3 knockdown, as shown by the inhibition of CDK2/p53 phosphorylation together with downregulation of BAX/Bcl-2 expression in HCC cells. Overall, these findings uncover the role of SKA3 in regulating the apoptosis and proliferation of hepatocellular carcinoma cells. This study was able to uncover new information on the tumorigenesis mechanism in hepatocellular carcinoma.", "claims": [{"id": "claim-method", "statement": "We acquired HCC expression data from GEO (datasets GSE62232, GSE45436, GSE36376, and GSE6764; http://www.ncbi.nlm.nih.gov/geo) and TCGA (http://gdc.cancer.gov/) databases. Log2 conversion was performed for all data in data standardization. EdgeR package was used to analyse gene differential expression for the data in count form. 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"N", "SKA3 expression", "P-Value"], ["Low (102)", "High (134)"], ["Sex", "", "", "", "0.244"], ["Male", "120", "55", "65", ""], ["Female", "116", "47", "69", ""], ["Age, years", "", "", "", "0.438"], ["<50", "139", "59", "80", ""], ["≥50", "97", "43", "54", ""], ["AFP, ng/L", "", "", "", "8.856e−11"], ["<200", "153", "89", "64", ""], ["≥200", "83", "13", "70", ""], ["HBsAg", "", "", "", "0.398"], ["Negative", "82", "34", "48", ""], ["Positive", "154", "68", "86", ""], ["Tumor size, cm", "", "", "", "3.29e–11"], ["≤5", "138", "84", "54", ""], [">5", "98", "18", "80", ""], ["Tumor nodule number", "", "", "", "8.29e−07"], ["Solitary", "146", "81", "65", ""], ["Multiple (≥2)", "90", "21", "69", ""], ["Cancer embolus", "", "", "", "5.83e−14"], ["Absence", "152", "92", "60", ""], ["Presence", "84", "10", "74", ""], ["TNM stage", "", "", "", "1.6e−05"], ["Early (I & II)", "157", "83", "74", ""], ["Late (III & IV)", "79", "19", "60", ""], ["Differentiation grade", "", "", "", "0.002"], ["Well", "173", "85", "88", ""], ["Poor", "63", "17", "46", ""], ["P53 expression", "", "", "", "0.021"], ["High", "95", "33", "62", ""], ["Low", "141", "69", "72", ""]], "row_count": 32, "column_count": 5, "numeric_cells": 80, "header_rows": 2, "locator": "section[3]/table-wrap[1]#Tab1"}}, {"id": "asset:table:pmid:31804459:2", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:0afa91a3ec149fd18d1d864d734b8ee24212e7d803e2954b2961552b8f661c39", "bytes": 1307, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[26]/table-wrap[1]#Tab2", "version": null, "note": "Univariate and multivariate Cox regression analysis of risk factors associated with overall survival.", "structure": {"pmcid": "PMC6895034", "section_index": 26, "section_title": "Overexpression of SKA3 in HCC patients predicts poor survival", "row_count": 12, "column_count": 7}, "table": {"label": "Table 2", "caption": "Univariate and multivariate Cox regression analysis of risk factors associated with overall survival.", "rows": [["Variables", "Univariate analysis", "Multivariate analysis"], ["HR", "95% CI", "P-Value", "HR", "95% CI", "P-Value"], ["SKA3 expression (high vs. low)", "2.239", "1.574–3.187", "7.59e−06", "1.299", "0.829–2.034", "0.25"], ["Sex (male vs. female)", "0.935", "0.67–1.305", "0.69", "", "", ""], ["Age (≥50 vs. <50)", "0.899", "0.659–1.226", "0.50", "", "", ""], ["HBsAg (positive vs. negative)", "0.944", "0.671–1.329", "0.74", "", "", ""], ["AFP (≥200 ng/ml vs. <200 ng/ml)", "1.797", "1.279–2.525", "7.31e−04", "1.048", "0.692–1.586", "0.83"], ["Tumor size (>5 cm vs. ≤5 cm)", "2.441", "1.742–3.421", "2.19e−07", "1.688", "1.136–2.509", "0.0095"], ["Tumor nodule number (multiple vs. single)", "1.797", "1.284–2.514", "6.27e−04", "1.086", "0.744–1.585", "0.67"], ["Cancer embolus (presence vs. absence)", "2.875", "2.035–4.061", "2.07e−09", "1.878", "1.231–2.866", "0.0035"], ["TNM stage (late vs. early)", "2.095", "1.485–2.956", "2.5e−05", "1.209", "0.804–1.818", "0.36"], ["Differentiation grade (poor vs. well)", "1.545", "1.08–2.211", "0.017", "0.970", "0.648–1.452", "0.88"]], "row_count": 12, "column_count": 7, "numeric_cells": 56, "header_rows": 2, "locator": "section[26]/table-wrap[1]#Tab2"}}, {"id": "asset:table:pmid:31804459:3", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:f84668530aca17eb0cb22a5431bf986381a66a472dc6915f59328b4eb0e643df", "bytes": 1326, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[26]/table-wrap[2]#Tab3", "version": null, "note": "Univariate and multivariate Cox regression analysis of risk factors associated with disease-free survival.", "structure": {"pmcid": "PMC6895034", "section_index": 26, "section_title": "Overexpression of SKA3 in HCC patients predicts poor survival", "row_count": 12, "column_count": 7}, "table": {"label": "Table 3", "caption": "Univariate and multivariate Cox regression analysis of risk factors associated with disease-free survival.", "rows": [["Variables", "Univariate analysis", "Multivariate analysis"], ["HR", "95% CI", "P-Value", "HR", "95% CI", "P-Value"], ["SKA3expression (high vs. low)", "2.107", "1.54–2.883", "3.18e−06", "1.501", "1.017–2.216", "0.04"], ["Sex (male vs. female)", "1.107", "0.818–1.498", "0.51", "", "", ""], ["Age (≥50 vs. <50)", "0.912", "0.67–1.24", "0.56", "", "", ""], ["HBsAg (positive vs. negative)", "1.441", "1.04–1.998", "0.028", "1.745", "1.234–2.466", "0.0016"], ["AFP (≥200 ng/ml vs. <200 ng/ml)", "1.623", "1.184–2.225", "2.63e−03", "1.042", "0.707–1.536", "0.83"], ["Tumor size (>5 cm vs. ≤5 cm)", "2.098", "1.549–2.84", "1.66e−06", "1.667", "1.174–2.365", "0.0042"], ["Tumor nodule number (multiple vs. single)", "1.517", "1.114–2.066", "8.13e−03", "1.077", "0.76–1.525", "0.68"], ["Cancer embolus (presence vs. absence)", "2.420", "1.766–3.316", "3.88e−08", "2.002", "1.046–3.832", "0.0362"], ["TNM stage (late vs. early)", "1.451", "1.049–2.008", "0.025", "1.051", "0.715–1.547", "0.80"], ["Differentiation grade (poor vs. well)", "1.480", "1.064–2.058", "0.02", "0.909", "0.62–1.333", "0.62"]], "row_count": 12, "column_count": 7, "numeric_cells": 59, "header_rows": 2, "locator": "section[26]/table-wrap[2]#Tab3"}}], "gaps": ["asset:data:geo:GSE36376 not downloaded", "asset:data:geo:GSE36376 licence not read", "asset:data:geo:GSE45436 not downloaded", "asset:data:geo:GSE45436 licence not read", "asset:data:geo:GSE62232 not downloaded", "asset:data:geo:GSE62232 licence not read", "asset:data:geo:GSE6764 not downloaded", "asset:data:geo:GSE6764 licence not read"]}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "family": "differential_expression", "specific": "edger", "label": "Differential expression analysis", "dsl_operations": ["normalise_counts", 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Log2 conversion was performed for all data in data standardization. EdgeR package was used to analyse gene differential expression for the data in count form. Limma package was used for the data in GEO database.\nWe selected genes whose |logFC (fold change)| > 1 and p-value < 0.05 as differential expression genes."}}, {"id": "method-2", "family": "survival_analysis", "specific": "cox_proportional_hazards", "label": "Survival analysis", "dsl_operations": ["cox_ph"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["time_to_event_with_censoring"], "evidence": {"score": 0.8, "band": "high", "quote": "Cox proportional hazards"}}, {"id": "method-3", "family": "differential_expression", "specific": "limma_voom", "label": "Differential expression analysis", "dsl_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["count_matrix_with_condition"], "evidence": {"score": 0.8, "band": "high", "quote": "Limma"}}, {"id": "method-4", "family": "correlation_analysis", "specific": "pearson", "label": "Correlation analysis", "dsl_operations": ["pearson_r"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["paired_numeric_columns"], "evidence": {"score": 0.8, "band": "high", "quote": "Pearson correlation"}}], "targets": [], "gaps": ["method.reader_differs_from_extractor"]}, "capability": {"state": "complete", "requirements": [{"capability_id": "capability:computational_analysis", "label": "Computational analysis platform", "assay_families": ["meta_analysis", "machine_learning", "survival_analysis", "statistical_regression", "pca", "molecular_docking", "network_analysis", "differential_expression", "gwas"], "availability_state": "owned", "tier_unlocked": "R1", "candidate": "Automated Assays Laravel application and simulated adapters"}], "gaps": []}, "readiness": {"state": "complete", "tier": "R1", "blocking_axis": "none", "blocked_on": "nothing:replicable_now", "axes": {"method": {"tier": "R1", "expressible": true, "required_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: edger."}, "capability": {"tier": "R1", "capability_id": "capability:computational_analysis", "availability_state": "owned", "basis": "The computational analysis is owned. The physical bench the paper used is not, so a physical validation cannot be run here."}, "data": {"tier": "R1", "reachable": true, "accessions": ["GSE62232", "GSE45436", "GSE36376", "GSE6764"], "resolved_accessions": ["GSE62232", "GSE45436", "GSE36376", "GSE6764"], "statements": ["The datasets used and/or analyzed during the current study can be obtained from the corresponding author on reasonable request."], "basis": "The paper names GSE62232, GSE45436, GSE36376, GSE6764 in Gene Expression Omnibus (GEO) and the accession resolves in the repository. No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "assets": ["source:pmid:31804459", "data:geo:GSE36376", "asset:table:pmid:31804459:1", "asset:table:pmid:31804459:2", "asset:table:pmid:31804459:3"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE36376"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-10-31T18:17:12Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 3, "usage": {"prompt_tokens": 33212, "completion_tokens": 1530, "cached_tokens": 792}}, "human_critique": null, "stages": [{"id": "extraction", "state": "complete", "reader": "MiniMax-M3.1-Flash", "provider": "minimax"}], "gaps": ["review.independent_reader", "review.machine_critique", "review.human_critique"]}, "execution": {"state": "absent", "status": "not_run", "mode": null, "runs": [], "gaps": ["execution.not_run"]}, "provenance": {"entities": [{"id": "pmid:31804459", "type": "paper", "label": "pmid:31804459"}, {"id": "source:pmid:31804459", "type": "manuscript", "label": "PMID 31804459 full text"}, {"id": "data:geo:GSE36376", "type": "dataset", "label": "GEO GSE36376"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:31804459", "type": "paper", "label": "pmid:31804459"}, {"id": "source:pmid:31804459", "type": "manuscript", "label": "PMID 31804459 full text"}, {"id": "data:geo:GSE36376", "type": "dataset", "label": "GEO GSE36376"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-31804459", "type": "extraction", "used": ["source:pmid:31804459"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE36376", "type": "accession_resolution", "used": ["data:geo:GSE36376"], "agent": "agent:corpus-assay-engine"}], "agents": [{"id": "agent:corpus-assay-engine", "type": "software", "label": "Corpus assay engine"}, {"id": "agent:minimax-reader", "type": "software", "label": "MiniMax literature reader"}], "source_run_id": "reading-sci-2026-11-01", "dsl_catalogue_fingerprint": "343fb30756ba6ec3", "capability_table_fingerprint": "2cb3e42f047d2ecf", "snapshot_id": "ba34b49490d9bfaf"}, "lineage": {"parent_id": "pmid:31804459", "parent_hash": "sha256:1eaa222c4d2b74dee430941ca109a11d546c1cc3a8dc040f78fb202666d23c55", "fork_of": null, "generation": 7}, "gaps": ["asset:data:geo:GSE36376 licence not read", "asset:data:geo:GSE36376 not downloaded", "asset:data:geo:GSE45436 licence not read", "asset:data:geo:GSE45436 not downloaded", "asset:data:geo:GSE62232 licence not read", "asset:data:geo:GSE62232 not downloaded", "asset:data:geo:GSE6764 licence not read", "asset:data:geo:GSE6764 not downloaded", "execution.not_run", "method.reader_differs_from_extractor", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "data_generation", "definition_id": "apoptosis_assay", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["nalysis (GSEA). G2/M phase arrest and severe apoptosis was also found to result from SKA3 knockdown", "s uncover the role of SKA3 in regulating the apoptosis and proliferation of hepatocellular carcinom", "lity was analyzed using Cell Counting Kit-8 (CCK8) assay and plate clone formation assay, whil"], "order_basis": "paper_text_order:569", "id": "assay:1"}, {"role": "data_generation", "definition_id": "animal_model", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["d to analyze cell invasion. The role of SKA3 in vivo was explored using subcutaneous xenotranspla", "tissues. Significant levels of inhibition of in vivo and in vitro tumor proliferation and invasio", "used to measure the mice, and at week 8 the mice were sacrificed. Thereafter, in order to analyze the presenc", "n order to perform cervical dislocation, the mice were euthanized. Then, the xenografts were remove"], "order_basis": "paper_text_order:721", "id": "assay:2"}, {"role": "data_generation", "definition_id": "ihc", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["on of SKA3 have a poor prognosis. Similarly, immunohistochemical staining of 236 samples of tumors also found", "ographed and preserved. Ki-67 antibodies for immunohistochemistry staining was obtained from Bioss (bs-2130R).", "SKA3 in HCC patients predicts poor survival Immunohistochemical results showed that 134 out of 236 HCC patie", "clinical patients (Fig. 1j, k). We then used immunohistochemical staining to explore the status of P53 in tho"], "order_basis": "paper_text_order:956", "id": "assay:3"}, {"role": "data_generation", "definition_id": "transfection", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["apoptosis was also found to result from SKA3 knockdown, as shown by the inhibition of CDK2/p53 phos", "boxplots and scatter plots. Cell culture and transfection Human hepatocellular carcinoma cell lines (L", "order to inhibit the expression of SKA3, we transfected three small interfering RNAs (siRNAs) target", "was mixed with pPACKH1 packaging plasmid and transfected into 293TN cells with sh-SKA3/NC. 3 days lat"], "order_basis": "paper_text_order:1454", "id": "assay:4"}, {"role": "data_generation", "definition_id": "cell_culture", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.77, "evidence": ["lar carcinoma cell lines (LM3 and HUH7) were cultured in American-type media (ATCC, Manassas, VA) at"], "order_basis": "paper_text_order:4554", "id": "assay:5"}, {"role": "analysis", "definition_id": "differential_expression", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["We acquired HCC expression data from GEO (datasets GSE62232, GSE45436, GSE36376, and GSE6764; http://www.ncbi.nlm.nih.gov/geo) and TCGA (http://gdc.cancer.gov/) databases. Log2 conversion was performed for all data in data standardization. EdgeR package was used to analyse gene differential expression for the data in count form. Limma package was used for the data in GEO database.\nWe selected genes whose |logFC (fold change)| > 1 and p-value < 0.05 as differential expression genes."], "order_basis": "consumes_earlier_output", "id": "assay:6"}]}