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pmid:32626741

Prognostic Value of Complement Component 2 and Its Correlation with Immune Infiltrates in Hepatocellular Carcinoma.

Gang Ning · Yan-Lin Huang · Li-Min Zhen · Wen-Xiong Xu · Xue-Jun Li · Li-Na Wu · Ying Liu · Chan Xie · Liang Peng

BioMed research international · 2020 doi:10.1155/2020/3765937

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Experiment

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Data

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title
Prognostic Value of Complement Component 2 and Its Correlation with Immune Infiltrates in Hepatocellular Carcinoma.
doi
10.1155/2020/3765937
pmid
32626741
authors array · 9 items
[0]
Gang Ning
[1]
Yan-Lin Huang
[2]
Li-Min Zhen
[3]
Wen-Xiong Xu
[4]
Xue-Jun Li
[5]
Li-Na Wu
[6]
Ying Liu
[7]
Chan Xie
[8]
Liang Peng
journal
BioMed research international
year
2020
abstract
BACKGROUND: Single nucleotide polymorphism (SNP) of complement component 2 (C2) has been found to be significantly associated with hepatocellular carcinoma (HCC). However, little is known about the role and mechanism of C2 in HCC. In the present study, we aimed to explore the prognostic value of C2 and its correlation with tumor-infiltrating immune cells in HCC. MATERIALS AND METHODS: mRNA expression was downloaded from TCGA (365 HCC patients and 50 healthy controls), GSE14520 (220 HCC patients and 220 adjacent normal tissues), and ICGC HCC (232 HCC patients) cohorts. Unpaired Student's t-tests or ANOVA tests were used to evaluate differences of C2 expression. Univariate and multivariate analyses were used to analyze the prognostic value of C2. CIBERSORT was used to calculate the proportion of 22 kinds of tumor-infiltrating immune cells. RESULTS: Significantly lower C2 expression was found at HCC compared to healthy controls, and C2 was associated with TNM stages. Higher C2 expression was significantly associated with better prognosis, and multivariate analysis showed that C2 was also an independent factor for the prognosis of HCC. Moreover, elevated CD4 T cells were found at HCC patients with higher C2 expression while the higher proportion of macrophage M0 cells was found in HCC patients with lower C2 expression. KEGG analysis showed that "cell cycle," "AMPK signaling pathway," and "PPAR signaling pathway" were enriched in HCC patients with higher C2 expression. CONCLUSION: C2 is a prognostic factor for HCC and may be used as a therapeutic target for future treatment of HCC.
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Data were presented as the median. Unpaired Student's t-tests or ANOVA tests were performed to compare the difference of C2 expression between HCC patients and healthy controls/adjacent normal tissues or among HCC patients with different histologic grades or TNM stages. Univariate and multivariate Cox regression analyses were carried out to analyze the prognostic value of C2 expression, and Kaplan-Meier analysis with a two-sided log-rank test was also performed to compare the OS of HCC patients with high or low C2 expression. Additional statistical analysis was performed with STAMP [14]. In the present study, a total of three cohorts, including the TCGA HCC cohort, GSE14520 HCC cohort, and ICGC HCC cohort, were employed. mRNA expression and corresponding clinical-pathological parameters of the TCGA HCC cohort were downloaded from TCGA (https://cancergenome.nih.gov/).
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sections[7] "2.5. Statistical Analysis" paragraph 2
quote
Data were presented as the median.
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sections[7] "2.5. Statistical Analysis" paragraph 2
quote
Unpaired Student's t-tests or ANOVA tests were performed to compare the difference of C2 expression between HCC patients and healthy controls/adjacent normal tissues or among HCC patients with different histologic grades or TNM stages.
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sections[7] "2.5. Statistical Analysis" paragraph 2
quote
Univariate and multivariate Cox regression analyses were carried out to analyze the prognostic value of C2 expression, and Kaplan-Meier analysis with a two-sided log-rank test was also performed to compare the OS of HCC patients with high or low C2 expression.
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sections[7] "2.5. Statistical Analysis" paragraph 2
quote
Additional statistical analysis was performed with STAMP [14].
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sections[4] "2.2. Acquisition of mRNA Expression and Corresponding Clinical-Pathological Parameters from TCGA, GEO, and ICGC" paragraph 2
quote
In the present study, a total of three cohorts, including the TCGA HCC cohort, GSE14520 HCC cohort, and ICGC HCC cohort, were employed. mRNA expression and corresponding clinical-pathological parameters of the TCGA HCC cohort were downloaded from TCGA (https://cancergenome.nih.gov/).
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All the data used in the present study could be downloaded from TCGA (https://cancergenome.nih.gov/), GEO (https://www.ncbi.nlm.nih.gov/geo/), and ICGC portal (https://dcc.icgc.org/projects/LIRI-JP).
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sections[18] "Data Availability" paragraph 2
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All the data used in the present study could be downloaded from TCGA (https://cancergenome.nih.gov/), GEO (https://www.ncbi.nlm.nih.gov/geo/), and ICGC portal (https://dcc.icgc.org/projects/LIRI-JP).
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GSM363424
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[452]
GSM363427
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GSM363428
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GSM363430
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GSM363431
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GSM363432
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GSM363433
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GSM363436
[462]
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GSM363438
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GSM363441
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GSM363442
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GSM363443
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GSM363444
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[473]
GSM363448
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GSM363450
[476]
GSM363451
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GSM712532
[478]
GSM712533
[479]
GSM712534
[480]
GSM712535
[481]
GSM712536
[482]
GSM712537
[483]
GSM712538
[484]
GSM712539
[485]
GSM712540
[486]
GSM712541
[487]
GSM712542
sample_count
488
group_sizes
null
group_sizes_basis
null
platform
3921;571
taxon
Homo sapiens
title
Gene expression data of human hepatocellular carcinoma (HCC)
resolution_checked_at
2026-11-01T15:39:54Z
resolution_check
identifier_resolution_only_no_download_no_licence_read
downloaded
false
licence_read
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asset:table:pmid:32626741:1
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Basic characteristics of HCC patients from the TCGA, GSE14520, and ICGC HCC cohorts.
structure object · 5 fields
pmcid
PMC7312969
section_index
4
section_title
2.2. Acquisition of mRNA Expression and Corresponding Clinical-Pathological Parameters from TCGA, GEO, and ICGC
row_count
9
column_count
4
table object · 8 fields
label
Table 1
caption
Basic characteristics of HCC patients from the TCGA, GSE14520, and ICGC HCC cohorts.
rows array · 9 items
[0] array · 4 items
[0]
Variables
[1]
TCGA cohort (N = 377)
[2]
GSE14520 cohort (N = 220)
[3]
ICGC cohort (N = 232)
[1] array · 4 items
[0]
Gender (male/female)
[1]
255/122
[2]
190/30
[3]
171/61
[2] array · 4 items
[0]
Age (years, median)
[1]
60 (16-90)
[2]
50 (21-77)
[3]
69 (31-89)
[3] array · 4 items
[0]
Cirrhosis (yes/no/NA)
[1]
81/137/159
[2]
202/18
[3]
NA
[4] array · 4 items
[0]
Histologic grade (G1/G2/G3/G4/NA)
[1]
55/180/124/13/5
[2]
NA
[3]
NA
[5] array · 4 items
[0]
TNM stage (I/II/III/IV/NA)
[1]
175/87/86/5/24
[2]
93/77/48/-/2
[3]
36/106/71/76
[6] array · 4 items
[0]
Main tumor size (>/≤5 cm)
[1]
NA
[2]
80/140
[3]
NA
[7] array · 4 items
[0]
Overall survival status (alive/dead)
[1]
245/132
[2]
136/84
[3]
189/43
[8] array · 4 items
[0]
Overall survival time (months, median)
[1]
19.67 (0-120.73)
[2]
51.65 (1.8-67.4)
[3]
26.0 (0.3-72)
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section[4]/table-wrap[1]#tab1
[3] object · 16 fields
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jats-table
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Univariate and multivariate analyses of C2 expression for overall survival in HCC patients of the TCGA cohort.
structure object · 5 fields
pmcid
PMC7312969
section_index
11
section_title
3.3. Prognostic Value of C2 in HCC Patients
row_count
8
column_count
7
table object · 8 fields
label
Table 2
caption
Univariate and multivariate analyses of C2 expression for overall survival in HCC patients of the TCGA cohort.
rows array · 8 items
[0] array · 3 items
[0]
Variables
[1]
Univariate analysis
[2]
Multivariate analysis
[1] array · 6 items
[0]
Hazard ratio
[1]
95% CI
[2]
p value
[3]
Hazard ratio
[4]
95% CI
[5]
p value
[2] array · 7 items
[0]
Gender (male vs. female)
[1]
0.82
[2]
0.57-1.16
[3]
0.26
[4]
[5]
[6]
[3] array · 7 items
[0]
Age (>60 vs. ≤60)
[1]
1.25
[2]
0.88-1.77
[3]
0.21
[4]
[5]
[6]
[4] array · 7 items
[0]
Cirrhosis (yes vs. no)
[1]
0.83
[2]
0.48-1.42
[3]
0.49
[4]
[5]
[6]
[5] array · 7 items
[0]
Histologic grade (G3+G4 vs. G1+G2)
[1]
1.12
[2]
0.78-1.61
[3]
0.54
[4]
[5]
[6]
[6] array · 7 items
[0]
TNM stage (III+IV vs. I+II)
[1]
2.43
[2]
1.69-3.55
[3]
0.000∗
[4]
2.38
[5]
1.64-3.46
[6]
0.000∗
[7] array · 7 items
[0]
C2 (high vs. low)
[1]
0.66
[2]
0.47-0.93
[3]
0.02∗
[4]
0.68
[5]
0.47-0.99
[6]
0.04∗
locator
section[11]/table-wrap[1]#tab2
[4] object · 16 fields
id
asset:table:pmid:32626741:3
role
table
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jats-table
media_type
application/vnd.jats.table+json
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null
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sha256:8779bd37d625daf2da9303a1a3ec50e1367f5456ea6a5c794b5fde2373e77a03
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read_table
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section[11]/table-wrap[2]#tab3
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null
note
Univariate and multivariate analysis of C2 expression for overall survival in HCC patients of the GSE14520 cohort.
structure object · 5 fields
pmcid
PMC7312969
section_index
11
section_title
3.3. Prognostic Value of C2 in HCC Patients
row_count
8
column_count
7
table object · 8 fields
label
Table 3
caption
Univariate and multivariate analysis of C2 expression for overall survival in HCC patients of the GSE14520 cohort.
rows array · 8 items
[0] array · 3 items
[0]
Variables
[1]
Univariate analysis
[2]
Multivariate analysis
[1] array · 6 items
[0]
Hazard ratio
[1]
95% CI
[2]
p value
[3]
Hazard ratio
[4]
95% CI
[5]
p value
[2] array · 7 items
[0]
Gender (male vs. female)
[1]
1.68
[2]
0.81-3.49
[3]
0.16
[4]
[5]
[6]
[3] array · 7 items
[0]
Age (>50 vs. ≤50)
[1]
1.0
[2]
0.65-1.53
[3]
0.99
[4]
[5]
[6]
[4] array · 7 items
[0]
Cirrhosis (yes vs. no)
[1]
4.57
[2]
1.13-18.62
[3]
0.03∗
[4]
3.66
[5]
0.89-14.98
[6]
0.07
[5] array · 7 items
[0]
Main tumor size (>5 cm vs. ≤5 cm)
[1]
1.97
[2]
1.28-3.30
[3]
0.002∗
[4]
1.18
[5]
0.69-2.01
[6]
0.56
[6] array · 7 items
[0]
TNM stage (III+IV vs. I+II)
[1]
3.43
[2]
2.20-6.11
[3]
0.000∗
[4]
2.38
[5]
1.64-3.46
[6]
0.000∗
[7] array · 7 items
[0]
C2 (high vs. low)
[1]
0.56
[2]
0.36-0.87
[3]
0.01∗
[4]
0.73
[5]
0.47-1.16
[6]
0.18
locator
section[11]/table-wrap[2]#tab3
[5] object · 16 fields
id
asset:table:pmid:32626741:4
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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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sha256:5843b5063bdf1fe83cfcd8421ee18868333e6d2b79e8393903bbc5e5cc935e98
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read_table
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section[11]/table-wrap[3]#tab4
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null
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Univariate and multivariate analyses of C2 expression for overall survival in HCC patients of the ICGC cohort.
structure object · 5 fields
pmcid
PMC7312969
section_index
11
section_title
3.3. Prognostic Value of C2 in HCC Patients
row_count
6
column_count
7
table object · 8 fields
label
Table 4
caption
Univariate and multivariate analyses of C2 expression for overall survival in HCC patients of the ICGC cohort.
rows array · 6 items
[0] array · 3 items
[0]
Variables
[1]
Univariate analysis
[2]
Multivariate analysis
[1] array · 6 items
[0]
Hazard ratio
[1]
95% CI
[2]
p value
[3]
Hazard ratio
[4]
95% CI
[5]
p value
[2] array · 7 items
[0]
Gender (male vs. female)
[1]
0.51
[2]
0.28-0.97
[3]
0.04∗
[4]
0.43
[5]
0.23-0.81
[6]
0.01∗
[3] array · 7 items
[0]
Age (>70 vs. ≤70)
[1]
1.06
[2]
0.58-1.94
[3]
0.84
[4]
[5]
[6]
[4] array · 7 items
[0]
TNM stage (III+IV vs. I+II)
[1]
2.38
[2]
1.30-4.36
[3]
0.004∗
[4]
2.59
[5]
1.39-4.80
[6]
0.003∗
[5] array · 7 items
[0]
C2 (high vs. low)
[1]
0.46
[2]
0.25-0.86
[3]
0.02∗
[4]
0.73
[5]
0.27-0.96
[6]
0.04∗
locator
section[11]/table-wrap[3]#tab4
[6] object · 16 fields
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asset:table:pmid:32626741:5
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table
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jats-table
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application/vnd.jats.table+json
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section[13]/table-wrap[1]#tab5
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null
note
Overlap of significant KEGG pathways enriched in HCC patients with higher C2 expression from the TCGA, GSE14520, and ICGC HCC cohorts.
structure object · 5 fields
pmcid
PMC7312969
section_index
13
section_title
3.5. Molecular Mechanisms of C2 in HCC
row_count
19
column_count
8
table object · 8 fields
label
Table 5
caption
Overlap of significant KEGG pathways enriched in HCC patients with higher C2 expression from the TCGA, GSE14520, and ICGC HCC cohorts.
rows array · 19 items
[0] array · 5 items
[0]
ID
[1]
Description
[2]
TCGA cohort
[3]
GSE14520 cohort
[4]
ICGC cohort
[1] array · 6 items
[0]
Count
[1]
p.adjust
[2]
Count
[3]
p.adjust
[4]
Count
[5]
p.adjust
[2] array · 8 items
[0]
hsa04110
[1]
Cell cycle
[2]
96
[3]
0.000
[4]
33
[5]
0.003
[6]
89
[7]
0.000
[3] array · 8 items
[0]
hsa04610
[1]
Complement and coagulation cascades
[2]
59
[3]
0.000
[4]
42
[5]
0.000
[6]
64
[7]
0.000
[4] array · 8 items
[0]
hsa04152
[1]
AMPK signaling pathway
[2]
61
[3]
0.023
[4]
34
[5]
0.001
[6]
58
[7]
0.031
[5] array · 8 items
[0]
hsa03320
[1]
PPAR signaling pathway
[2]
42
[3]
0.014
[4]
27
[5]
0.000
[6]
40
[7]
0.025
[6] array · 8 items
[0]
hsa04910
[1]
Insulin signaling pathway
[2]
80
[3]
0.000
[4]
28
[5]
0.008
[6]
66
[7]
0.026
[7] array · 8 items
[0]
hsa01200
[1]
Carbon metabolism
[2]
73
[3]
0.000
[4]
44
[5]
0.000
[6]
71
[7]
0.000
[8] array · 8 items
[0]
hsa00630
[1]
Glyoxylate and dicarboxylate metabolism
[2]
20
[3]
0.012
[4]
13
[5]
0.002
[6]
21
[7]
0.004
[9] array · 8 items
[0]
hsa00620
[1]
Pyruvate metabolism
[2]
27
[3]
0.001
[4]
13
[5]
0.017
[6]
25
[7]
0.006
[10] array · 8 items
[0]
hsa01230
[1]
Biosynthesis of amino acids
[2]
42
[3]
0.011
[4]
33
[5]
0.000
[6]
48
[7]
0.000
[11] array · 8 items
[0]
hsa00410
[1]
Beta-alanine metabolism
[2]
19
[3]
0.039
[4]
11
[5]
0.021
[6]
19
[7]
0.030
[12] array · 8 items
[0]
hsa00270
[1]
Cysteine and methionine metabolism
[2]
29
[3]
0.017
[4]
16
[5]
0.008
[6]
29
[7]
0.012
[13] array · 8 items
[0]
hsa05110
[1]
Vibrio cholerae infection
[2]
31
[3]
0.006
[4]
17
[5]
0.004
[6]
35
[7]
0.000
[14] array · 8 items
[0]
hsa00010
[1]
Glycolysis/gluconeogenesis
[2]
42
[3]
0.001
[4]
22
[5]
0.002
[6]
36
[7]
0.029
[15] array · 8 items
[0]
hsa04979
[1]
Cholesterol metabolism
[2]
36
[3]
0.000
[4]
19
[5]
0.001
[6]
37
[7]
0.000
[16] array · 8 items
[0]
hsa00280
[1]
Valine, leucine, and isoleucine degradation
[2]
27
[3]
0.042
[4]
19
[5]
0.000
[6]
27
[7]
0.029
[17] array · 8 items
[0]
hsa00640
[1]
Propanoate metabolism
[2]
21
[3]
0.027
[4]
54
[5]
0.000
[6]
20
[7]
0.041
[18] array · 8 items
[0]
hsa00260
[1]
Glycine, serine, and threonine metabolism
[2]
23
[3]
0.048
[4]
16
[5]
0.001
[6]
26
[7]
0.004
locator
section[13]/table-wrap[1]#tab5
gaps array · 2 items
[0]
asset:data:geo:GSE14520 not downloaded
[1]
asset:data:geo:GSE14520 licence not read
analysis object · 4 fields
state
complete
methods array · 4 items
[0] object · 10 fields
id
method-1
family
group_comparison
specific
anova
label
Group comparison
dsl_operations array · 4 items
[0]
group_summary
[1]
welch_t
[2]
bootstrap_mean_difference
[3]
group_comparison_anova
missing_operations array · 0 items
parameters object · 0 fields
data_shapes array · 1 item
[0]
two_or_more_groups_continuous
evidence object · 3 fields
score
1
band
reordered
quote
Data were presented as the median. Unpaired Student's t-tests or ANOVA tests were performed to compare the difference of C2 expression between HCC patients and healthy controls/adjacent normal tissues or among HCC patients with different histologic grades or TNM stages. Univariate and multivariate Cox regression analyses were carried out to analyze the prognostic value of C2 expression, and Kaplan-Meier analysis with a two-sided log-rank test was also performed to compare the OS of HCC patients with high or low C2 expression. Additional statistical analysis was performed with STAMP [14]. In the present study, a total of three cohorts, including the TCGA HCC cohort, GSE14520 HCC cohort, and ICGC HCC cohort, were employed. mRNA expression and corresponding clinical-pathological parameters of the TCGA HCC cohort were downloaded from TCGA (https://cancergenome.nih.gov/).
[1] object · 10 fields
id
method-2
family
survival_analysis
specific
kaplan_meier
label
Survival analysis
dsl_operations array · 1 item
[0]
survival_km
missing_operations array · 0 items
parameters object · 0 fields
data_shapes array · 1 item
[0]
time_to_event_with_censoring
evidence object · 3 fields
score
0.8
band
high
quote
Kaplan-Meier
[2] object · 10 fields
id
method-3
family
survival_analysis
specific
cox_proportional_hazards
label
Survival analysis
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[0]
cox_ph
missing_operations array · 0 items
parameters object · 0 fields
data_shapes array · 1 item
[0]
time_to_event_with_censoring
evidence object · 3 fields
score
0.8
band
high
quote
Cox regression
[3] object · 10 fields
id
method-4
family
survival_analysis
specific
log_rank_test
label
Survival analysis
dsl_operations array · 1 item
[0]
logrank_test
missing_operations array · 0 items
parameters object · 0 fields
data_shapes array · 1 item
[0]
time_to_event_with_censoring
evidence object · 3 fields
score
0.8
band
high
quote
log-rank
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gaps array · 0 items
capability object · 3 fields
state
complete
requirements array · 1 item
[0] object · 6 fields
capability_id
capability:computational_analysis
label
Computational analysis platform
assay_families array · 9 items
[0]
meta_analysis
[1]
machine_learning
[2]
survival_analysis
[3]
statistical_regression
[4]
pca
[5]
molecular_docking
[6]
network_analysis
[7]
differential_expression
[8]
gwas
candidate
Automated Assays Laravel application and simulated adapters
gaps array · 0 items
readiness object · 8 fields
state
complete
tier
R1
blocked_on
nothing:replicable_now
axes object · 3 fields
method object · 5 fields
tier
R1
expressible
true
required_operations array · 4 items
[0]
group_summary
[1]
welch_t
[2]
bootstrap_mean_difference
[3]
group_comparison_anova
missing_operations array · 0 items
basis
The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: anova.
capability object · 4 fields
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 object · 6 fields
tier
R1
reachable
true
accessions array · 1 item
[0]
GSE14520
resolved_accessions array · 1 item
[0]
GSE14520
statements array · 1 item
[0]
All the data used in the present study could be downloaded from TCGA (https://cancergenome.nih.gov/), GEO (https://www.ncbi.nlm.nih.gov/geo/), and ICGC portal (https://dcc.icgc.org/projects/LIRI-JP).
basis
The paper names GSE14520 in Gene Expression Omnibus (GEO) and the accession resolves in the repository. No dataset was downloaded and no licence was read.
can_run object · 3 fields
dsl_operations array · 4 items
[0]
group_summary
[1]
welch_t
[2]
bootstrap_mean_difference
[3]
group_comparison_anova
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[0]
source:pmid:32626741
[1]
data:geo:GSE14520
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asset:table:pmid:32626741:1
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asset:table:pmid:32626741:2
[4]
asset:table:pmid:32626741:3
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asset:table:pmid:32626741:4
[6]
asset:table:pmid:32626741:5
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[0]
run_analysis
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data_gaps array · 1 item
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data:geo:GSE14520
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review object · 5 fields
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partial
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extraction_review
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MiniMax-M3.1-Flash
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minimax
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minimax
read_at
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independence
single_reader
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reordered
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verbatim
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3
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prompt_tokens
27570
completion_tokens
1841
cached_tokens
784
stages array · 1 item
[0] object · 4 fields
id
extraction
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complete
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MiniMax-M3.1-Flash
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minimax
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review.independent_reader
[1]
review.machine_critique
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review.human_critique
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absent
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not_run
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null
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gaps array · 1 item
[0]
execution.not_run
provenance object · 7 fields
entities array · 3 items
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Data were presented as the median. Unpaired Student's t-tests or ANOVA tests were performed to compare the difference of C2 expression between HCC patients and healthy controls/adjacent normal tissues or among HCC patients with different histologic grades or TNM stages. Univariate and multivariate Cox regression analyses were carried out to analyze the prognostic value of C2 expression, and Kaplan-Meier analysis with a two-sided log-rank test was also performed to compare the OS of HCC patients with high or low C2 expression. Additional statistical analysis was performed with STAMP [14]. In the present study, a total of three cohorts, including the TCGA HCC cohort, GSE14520 HCC cohort, and ICGC HCC cohort, were employed. mRNA expression and corresponding clinical-pathological parameters of the TCGA HCC cohort were downloaded from TCGA (https://cancergenome.nih.gov/).
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{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:32626741", "kind": "science-record", "revision": 8, "content_hash": "sha256:73a523d17c522dd2fd1b4eca7bde218dcbb95d4051f0806390eaff49f294d3f3", "created_at": "2026-11-01T15:41:05Z", "updated_at": "2026-11-01T22:45:03Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Prognostic Value of Complement Component 2 and Its Correlation with Immune Infiltrates in Hepatocellular Carcinoma.", "doi": "10.1155/2020/3765937", "pmid": "32626741", "authors": ["Gang Ning", "Yan-Lin Huang", "Li-Min Zhen", "Wen-Xiong Xu", "Xue-Jun Li", "Li-Na Wu", "Ying Liu", "Chan Xie", "Liang Peng"], "journal": "BioMed research international", "year": 2020, "abstract": "BACKGROUND: Single nucleotide polymorphism (SNP) of complement component 2 (C2) has been found to be significantly associated with hepatocellular carcinoma (HCC). However, little is known about the role and mechanism of C2 in HCC. In the present study, we aimed to explore the prognostic value of C2 and its correlation with tumor-infiltrating immune cells in HCC.\nMATERIALS AND METHODS: mRNA expression was downloaded from TCGA (365 HCC patients and 50 healthy controls), GSE14520 (220 HCC patients and 220 adjacent normal tissues), and ICGC HCC (232 HCC patients) cohorts. Unpaired Student's t-tests or ANOVA tests were used to evaluate differences of C2 expression. Univariate and multivariate analyses were used to analyze the prognostic value of C2. CIBERSORT was used to calculate the proportion of 22 kinds of tumor-infiltrating immune cells.\nRESULTS: Significantly lower C2 expression was found at HCC compared to healthy controls, and C2 was associated with TNM stages. Higher C2 expression was significantly associated with better prognosis, and multivariate analysis showed that C2 was also an independent factor for the prognosis of HCC. Moreover, elevated CD4 T cells were found at HCC patients with higher C2 expression while the higher proportion of macrophage M0 cells was found in HCC patients with lower C2 expression. KEGG analysis showed that \"cell cycle,\" \"AMPK signaling pathway,\" and \"PPAR signaling pathway\" were enriched in HCC patients with higher C2 expression.\nCONCLUSION: C2 is a prognostic factor for HCC and may be used as a therapeutic target for future treatment of HCC.", "claims": [{"id": "claim-method", "statement": "Data were presented as the median. Unpaired Student's t-tests or ANOVA tests were performed to compare the difference of C2 expression between HCC patients and healthy controls/adjacent normal tissues or among HCC patients with different histologic grades or TNM stages. Univariate and multivariate Cox regression analyses were carried out to analyze the prognostic value of C2 expression, and Kaplan-Meier analysis with a two-sided log-rank test was also performed to compare the OS of HCC patients with high or low C2 expression. Additional statistical analysis was performed with STAMP [14]. In the present study, a total of three cohorts, including the TCGA HCC cohort, GSE14520 HCC cohort, and ICGC HCC cohort, were employed. mRNA expression and corresponding clinical-pathological parameters of the TCGA HCC cohort were downloaded from TCGA (https://cancergenome.nih.gov/).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:32626741", "locator": "sections[7] \"2.5. Statistical Analysis\" paragraph 2", "quote": "Data were presented as the median."}, {"asset": "source:pmid:32626741", "locator": "sections[7] \"2.5. 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Acquisition of mRNA Expression and Corresponding Clinical-Pathological Parameters from TCGA, GEO, and ICGC\" paragraph 2", "quote": "In the present study, a total of three cohorts, including the TCGA HCC cohort, GSE14520 HCC cohort, and ICGC HCC cohort, were employed. mRNA expression and corresponding clinical-pathological parameters of the TCGA HCC cohort were downloaded from TCGA (https://cancergenome.nih.gov/)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "All the data used in the present study could be downloaded from TCGA (https://cancergenome.nih.gov/), GEO (https://www.ncbi.nlm.nih.gov/geo/), and ICGC portal (https://dcc.icgc.org/projects/LIRI-JP).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:32626741", "locator": "sections[18] \"Data Availability\" paragraph 2", "quote": "All the data used in the present study could be downloaded from TCGA (https://cancergenome.nih.gov/), GEO (https://www.ncbi.nlm.nih.gov/geo/), and ICGC portal (https://dcc.icgc.org/projects/LIRI-JP)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": null, "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:32626741"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. 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Prognostic Value of C2 in HCC Patients", "row_count": 6, "column_count": 7}, "table": {"label": "Table 4", "caption": "Univariate and multivariate analyses of C2 expression for overall survival in HCC patients of the ICGC cohort.", "rows": [["Variables", "Univariate analysis", "Multivariate analysis"], ["Hazard ratio", "95% CI", "p value", "Hazard ratio", "95% CI", "p value"], ["Gender (male vs. female)", "0.51", "0.28-0.97", "0.04∗", "0.43", "0.23-0.81", "0.01∗"], ["Age (>70 vs. ≤70)", "1.06", "0.58-1.94", "0.84", "", "", ""], ["TNM stage (III+IV vs. I+II)", "2.38", "1.30-4.36", "0.004∗", "2.59", "1.39-4.80", "0.003∗"], ["C2 (high vs. low)", "0.46", "0.25-0.86", "0.02∗", "0.73", "0.27-0.96", "0.04∗"]], "row_count": 6, "column_count": 7, "numeric_cells": 24, "header_rows": 2, "locator": "section[11]/table-wrap[3]#tab4"}}, {"id": "asset:table:pmid:32626741:5", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:a4550f88bc07e1ef9d3ba17bc008d12b5c5220c1489279ea2f56fb64e9ef09e8", "bytes": 1798, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[13]/table-wrap[1]#tab5", "version": null, "note": "Overlap of significant KEGG pathways enriched in HCC patients with higher C2 expression from the TCGA, GSE14520, and ICGC HCC cohorts.", "structure": {"pmcid": "PMC7312969", "section_index": 13, "section_title": "3.5. 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Unpaired Student's t-tests or ANOVA tests were performed to compare the difference of C2 expression between HCC patients and healthy controls/adjacent normal tissues or among HCC patients with different histologic grades or TNM stages. Univariate and multivariate Cox regression analyses were carried out to analyze the prognostic value of C2 expression, and Kaplan-Meier analysis with a two-sided log-rank test was also performed to compare the OS of HCC patients with high or low C2 expression. Additional statistical analysis was performed with STAMP [14]. In the present study, a total of three cohorts, including the TCGA HCC cohort, GSE14520 HCC cohort, and ICGC HCC cohort, were employed. mRNA expression and corresponding clinical-pathological parameters of the TCGA HCC cohort were downloaded from TCGA (https://cancergenome.nih.gov/)."}}, {"id": "method-2", "family": "survival_analysis", "specific": "kaplan_meier", "label": "Survival analysis", "dsl_operations": ["survival_km"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["time_to_event_with_censoring"], "evidence": {"score": 0.8, "band": "high", "quote": "Kaplan-Meier"}}, {"id": "method-3", "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 regression"}}, {"id": "method-4", "family": "survival_analysis", "specific": "log_rank_test", "label": "Survival analysis", "dsl_operations": ["logrank_test"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["time_to_event_with_censoring"], "evidence": {"score": 0.8, "band": "high", "quote": "log-rank"}}], "targets": [], "gaps": []}, "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": ["group_summary", "welch_t", "bootstrap_mean_difference", "group_comparison_anova"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: anova."}, "capability": {"tier": "R1", "capability_id": "capability:computational_analysis", "availability_state": "owned", "basis": "The computational analysis is owned. 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