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pmid:30755830

Identification of special key genes for alcohol-related hepatocellular carcinoma through bioinformatic analysis.

Xiuzhi Zhang · Chunyan Kang · Ningning Li · Xiaoli Liu · Jinzhong Zhang · Fenglan Gao · Liping Dai

PeerJ · 2019 doi:10.7717/peerj.6375

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Record details sci_version · id · kind · revision · content_hash · schema · created_at · updated_at · generator
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pmid:30755830
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science-record
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sha256:86ec1ea3a35dc7fc3188ddc7f2ead76c5f23fa75336c99f031140cb49127d9e7
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https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json
created_at
2026-11-01T15:40:42Z
updated_at
2026-11-01T22:43:48Z
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paper object · 10 fields
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title
Identification of special key genes for alcohol-related hepatocellular carcinoma through bioinformatic analysis.
doi
10.7717/peerj.6375
pmid
30755830
authors array · 7 items
[0]
Xiuzhi Zhang
[1]
Chunyan Kang
[2]
Ningning Li
[3]
Xiaoli Liu
[4]
Jinzhong Zhang
[5]
Fenglan Gao
[6]
Liping Dai
journal
PeerJ
year
2019
abstract
BACKGROUND: Alcohol-related hepatocellular carcinoma (HCC) was reported to be diagnosed at a later stage, but the mechanism was unknown. This study aimed to identify special key genes (SKGs) during alcohol-related HCC development and progression. METHODS: The mRNA data of 369 HCC patients and the clinical information were downloaded from the Cancer Genome Atlas project (TCGA). The 310 patients with certain HCC-related risk factors were included for analysis and divided into seven groups according to the risk factors. Survival analyses were applied for the HCC patients of different groups. The patients with hepatitis B virus or hepatitis C virus infection only were combined into the HCC-V group for further analysis. The differentially expressed genes (DEGs) between the HCCs with alcohol consumption only (HCC-A) and HCC-V tumors were identified through limma package in R with cutoff criteria│log2 fold change (logFC)|>1.0 and p < 0.05. The DEGs between eight alcohol-related HCCs and their paired normal livers of GSE59259 from the Gene Expression Omnibus (GEO) were identified through GEO2R (a built-in tool in GEO database) with cutoff criteria |logFC|> 2.0 and adj.p < 0.05. The intersection of the two sets of DEGs was considered SKGs which were then investigated for their specificity through comparisons between HCC-A and other four HCC groups. The SKGs were analyzed for their correlations with HCC-A stage and grade and their prognostic power for HCC-A patients. The expressional differences of the SKGs in the HCCs in whole were also investigated through Gene Expression Profiling Interactive Analysis (GEPIA). The SKGs in HCC were validated through Oncomine database analysis. RESULTS: Pathological stage is an independent prognostic factor for HCC patients. HCC-A patients were diagnosed later than HCC patients with other risk factors. Ten SKGs were identified and nine of them were confirmed for their differences in paired samples of HCC-A patients. Three (SLC22A10, CD5L, and UROC1) and four (SLC22A10, UROC1, CSAG3, and CSMD1) confirmed genes were correlated with HCC-A stage and grade, respectively. SPP2 had a lower trend in HCC-A tumors and was negatively correlated with HCC-A stage and grade. The SKGs each was differentially expressed between HCC-A and at least one of other HCC groups. CD5L was identified to be favorable prognostic factor for overall survival while CSMD1 unfavorable prognostic factor for disease-free survival for HCC-A patients and HCC patients in whole. Through Oncomine database, the dysregulations of the SKGs in HCC and their clinical significance were confirmed. CONCLUSION: The poor prognosis of HCC-A patients might be due to their later diagnosis. The SKGs, especially the four stage-correlated genes (CD5L, SLC22A10, UROC1, and SPP2) might play important roles in HCC development, especially alcohol-related HCC development and progression. CD5L might be useful for overall survival and CSMD1 for disease-free survival predication in HCC, especially alcohol-related HCC.
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The DEGs (DEGs-1) between HCC-A tumors and HCC-V tumors were identified with limma (Ritchie et al., 2015) package in R software.
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sections[6] "Identification of DEGs-1 (DEGs between HCC-A group and other HCC groups)" paragraph 2
quote
The DEGs (DEGs-1) between HCC-A tumors and HCC-V tumors were identified with limma (Ritchie et al., 2015) package in R software.
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The following information was supplied regarding data availability: raw data were generated in the study. All the original data in this study weredownloaded from the public databases including TCGA (https://portal.gdc.cancer.gov/), GEO (https://www.ncbi.nlm.nih.gov/geo/) and Oncomine (https://www.oncomine.org/). For the SKGs identification, we used TCGA-LIHC (https://portal.gdc.cancer.gov/projects/TCGA-LIHC) and GSE59259 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=gse59259). The HCC datasets from the Oncomine database (https://www.oncomine.org) were: Chen liver, Mas liver, Roessler liver, Roessler liver 2, Wurmbach liver, Jia liver, and Iizuka Liver 2.
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sections[33] "Data Availability Statement" paragraphs 1-5
quote
The following information was supplied regarding data availability: raw data were generated in the study. All the original data in this study weredownloaded from the public databases including TCGA (https://portal.gdc.cancer.gov/), GEO (https://www.ncbi.nlm.nih.gov/geo/) and Oncomine (https://www.oncomine.org/). For the SKGs identification, we used TCGA-LIHC (https://portal.gdc.cancer.gov/projects/TCGA-LIHC) and GSE59259 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=gse59259). The HCC datasets from the Oncomine database (https://www.oncomine.org) were: Chen liver, Mas liver, Roessler liver, Roessler liver 2, Wurmbach liver, Jia liver, and Iizuka Liver 2.
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The following information was supplied regarding data availability: raw data were generated in the study. All the original data in this study weredownloaded from the public databases including TCGA (https://portal.gdc.cancer.gov/), GEO (https://www.ncbi.nlm.nih.gov/geo/) and Oncomine (https://www.oncomine.org/). For the SKGs identification, we used TCGA-LIHC (https://portal.gdc.cancer.gov/projects/TCGA-LIHC) and GSE59259 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=gse59259). The HCC datasets from the Oncomine database (https://www.oncomine.org) were: Chen liver, Mas liver, Roessler liver, Roessler liver 2, Wurmbach liver, Jia liver, and Iizuka Liver 2.
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The following information was supplied regarding data availability: raw data were generated in the study. All the original data in this study weredownloaded from the public databases including TCGA (https://portal.gdc.cancer.gov/), GEO (https://www.ncbi.nlm.nih.gov/geo/) and Oncomine (https://www.oncomine.org/). For the SKGs identification, we used TCGA-LIHC (https://portal.gdc.cancer.gov/projects/TCGA-LIHC) and GSE59259 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=gse59259). The HCC datasets from the Oncomine database (https://www.oncomine.org) were: Chen liver, Mas liver, Roessler liver, Roessler liver 2, Wurmbach liver, Jia liver, and Iizuka Liver 2.
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Homo sapiens
title
Expression profiles in alcohol-associated hepatocellular carcinoma
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2026-11-01T15:39:54Z
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Clinicopathological characteristics of HCC patients# from TCGA database.
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Data processing and analysis of HCC patients from TCGA database
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Table 1
caption
Clinicopathological characteristics of HCC patients# from TCGA database.
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[0] array · 9 items
[0]
Variable
[1]
HCC-N (n = 91)
[2]
HCC-A (n = 68)
[3]
HCC-B (n = 74)
[4]
HCC-C (n = 32)
[5]
HCC-AB (n = 20)
[6]
HCC-AC (n = 14)
[7]
HCC-NAF (n = 11)
[8]
Total (n = 310)
[1] array · 9 items
[0]
Risk factors
[1]
None
[2]
Alcohol
[3]
HBV
[4]
HCV
[5]
HBV alcohol
[6]
HCV alcohol
[7]
Non-alcoholic fatty liver disease
[8]
[2] array · 2 items
[0]
Age at diagnosis (year)
[1]
p = 0.001
[3] array · 9 items
[0]
<60
[1]
39(42.6%)
[2]
23(33.8%)
[3]
50(67.6%)
[4]
13(40.6%)
[5]
13(65.0%)
[6]
6(42.9%)
[7]
3(27.3%)
[8]
[4] array · 9 items
[0]
≥60
[1]
52(57.4%)
[2]
45(66.2%)
[3]
24(32.4%)
[4]
19(59.4%)
[5]
7(35.0%)
[6]
8(57.1%)
[7]
8(72.7%)
[8]
[5] array · 2 items
[0]
Gender
[1]
p = 1.305E-13
[6] array · 9 items
[0]
Male
[1]
32(35.2%)
[2]
57(83.8%)
[3]
57(77.3%)
[4]
25(78.1%)
[5]
20(100%)
[6]
13(92.9%)
[7]
5(45.5%)
[8]
[7] array · 9 items
[0]
Female
[1]
59(64.8%)
[2]
11(16.2%)
[3]
17(22.7%)
[4]
7(21.9%)
[5]
0(0%)
[6]
1(7.1%)
[7]
6(54.5%)
[8]
[8] array · 2 items
[0]
Pathologic stage
[1]
p = 0.010
[9] array · 9 items
[0]
Stage I
[1]
30(33.0%)
[2]
20(22.0%)
[3]
46(62.3%)
[4]
16(50.0%)
[5]
15(75.0%)
[6]
9(64.3%)
[7]
5(45.4%)
[8]
[10] array · 9 items
[0]
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[1]
20(22.3%)
[2]
13(19.1%)
[3]
16(21.6%)
[4]
7(21.9%)
[5]
3(15%)
[6]
3(21.4%)
[7]
3(27.3%)
[8]
[11] array · 9 items
[0]
Stage III
[1]
33(36.2%)
[2]
25(36.8%)
[3]
7(9.4%)
[4]
5(15.6%)
[5]
2(10%)
[6]
1(7.1%)
[7]
0(0%)
[8]
[12] array · 9 items
[0]
Stage IV
[1]
1(1.1%)
[2]
1(1.5%)
[3]
2(2.7%)
[4]
0(0%)
[5]
0(0%)
[6]
0(0%)
[7]
0(0%)
[8]
[13] array · 9 items
[0]
NA
[1]
7(7.7%)
[2]
7(10.3%)
[3]
3(4.0%)
[4]
4(12.5%)
[5]
0(10%)
[6]
1(7.1%)
[7]
3(27.3)
[8]
[14] array · 2 items
[0]
Pathologic grade
[1]
p = 0.002
[15] array · 9 items
[0]
G1
[1]
13(14.3%)
[2]
10(14.7%)
[3]
6(8.1%)
[4]
7(21.9%)
[5]
5(25.0%)
[6]
4(28.6%)
[7]
2(18.2%)
[8]
[16] array · 9 items
[0]
G2
[1]
46(50.5%)
[2]
38(55.9%)
[3]
27(36.5%)
[4]
13(40.6%)
[5]
13(65.0%)
[6]
7(50%)
[7]
8(72.7%)
[8]
[17] array · 9 items
[0]
G3
[1]
27(29.7%)
[2]
19(27.9%)
[3]
33(44.6%)
[4]
9(28.1%)
[5]
2(10%)
[6]
3(21.4%)
[7]
1(9.1%)
[8]
[18] array · 9 items
[0]
G4
[1]
1(1.1%)
[2]
0(0%)
[3]
7(9.4%)
[4]
0(0%)
[5]
0(0%)
[6]
0(0%)
[7]
0(0%)
[8]
[19] array · 9 items
[0]
NA
[1]
4(4.4%)
[2]
1(1.5%)
[3]
1(1.4%)
[4]
3(9.4%)
[5]
0(0%)
[6]
0(0%)
[7]
0(0%)
[8]
[20] array · 2 items
[0]
Family history of cancer
[1]
p = 1.598E-4
[21] array · 9 items
[0]
None
[1]
43(47.3%)
[2]
45(66.2%)
[3]
53(71.6%)
[4]
14(43.7%)
[5]
18(96.0%)
[6]
7(50.0%)
[7]
5(45.5%)
[8]
[22] array · 9 items
[0]
Yes
[1]
42(46.1%)
[2]
12(17.6%)
[3]
14(18.9%)
[4]
7(21.9%)
[5]
2(4.0%)
[6]
6(42.9%)
[7]
6(54.5%)
[8]
[23] array · 9 items
[0]
NA
[1]
6(6.6%)
[2]
11(16.2%)
[3]
7(9.5%)
[4]
11(34.4%)
[5]
0(0%)
[6]
1(7.1%)
[7]
0(0%)
[8]
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Cox regression analysis (stepwise) of the variables# in HCC patients.
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PMC6368834
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13
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Pathological stage determines the overall and disease-free survival of HCC patients
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Table 2
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Cox regression analysis (stepwise) of the variables# in HCC patients.
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Prognostic factor
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B
[3]
SE
[4]
HR(95.0% CI)
[5]
p
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[0]
Overall survival§
[1]
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[3]
0.129
[4]
1.477(1.147–1.902)
[5]
0.003
[2] array · 6 items
[0]
Disease-free survival
[1]
Pathological stage
[2]
0.331
[3]
0.153
[4]
1.392(1.031–1.880)
[5]
0.031
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Comparison of pathological stages among different HCC groups.
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HCC-A patients are diagnosed later than HCC patients with other risk factors
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Table 3
caption
Comparison of pathological stages among different HCC groups.
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[0]
Group
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HCC-A
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HCC-N
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HCC-B
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HCC-C
[5]
HCC-AB
[6]
HCC-AC
[7]
HCC-NAF
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[9]
DF
[10]
p
[1] array · 11 items
[0]
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[1]
168.53
[2]
167.24
[3]
118.45
[4]
128.89
[5]
104.90
[6]
109.31
[7]
111.00
[8]
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[9]
6
[10]
1.429E-5**
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section[14]/table-wrap[2]#table-4
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Comparison of pathological stage between HCC-A patients and patients in other HCC groups.
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PMC6368834
section_index
14
section_title
HCC-A patients are diagnosed later than HCC patients with other risk factors
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3
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7
table object · 8 fields
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Table 4
caption
Comparison of pathological stage between HCC-A patients and patients in other HCC groups.
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[0]
HCC-A vs.
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HCC-N
[2]
HCC-B
[3]
HCC-C
[4]
HCC-AB
[5]
HCC-AC
[6]
HCC-NAF
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[0]
Z
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[2]
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[3]
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[4]
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[5]
−2.501
[6]
−2.068
[2] array · 7 items
[0]
p
[1]
0.884
[2]
1.852E-4**
[3]
0.023*
[4]
0.002*
[5]
0.012*
[6]
0.039*
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section[17]/table-wrap[1]#table-5
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Correlations analysis between SKGs and the pathological stage and grade of HCC-A tumors.
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PMC6368834
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17
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SKGs identification
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Table 5
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Correlations analysis between SKGs and the pathological stage and grade of HCC-A tumors.
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Variable
[1]
Correlation with pathological stage (n = 61)
[2]
Correlation with pathological grade (n = 67)
[1] array · 4 items
[0]
R
[1]
p value
[2]
R
[3]
p value
[2] array · 5 items
[0]
SLC22A10
[1]
−0.378
[2]
0.003**
[3]
−0.368
[4]
0.002**
[3] array · 5 items
[0]
CD5L
[1]
−0.333
[2]
0.009**
[3]
−0.160
[4]
0.196
[4] array · 5 items
[0]
UROC1
[1]
−0.320
[2]
0.012*
[3]
−0.346
[4]
0.004**
[5] array · 5 items
[0]
SPP2
[1]
−0.298
[2]
0.020*
[3]
−0.440
[4]
2.933E-7**
[6] array · 5 items
[0]
CSAG3
[1]
−0.162
[2]
0.211
[3]
0.289
[4]
0.018*
[7] array · 5 items
[0]
CSMD1
[1]
0.083
[2]
0.524
[3]
0.293
[4]
0.016*
[8] array · 5 items
[0]
MAGEA3
[1]
−0.062
[2]
0.635
[3]
0.138
[4]
0.266
[9] array · 5 items
[0]
IGF2
[1]
−0.032
[2]
0.806
[3]
−0.151
[4]
0.221
[10] array · 5 items
[0]
CSAG1
[1]
−0.025
[2]
0.850
[3]
0.214
[4]
0.082
[11] array · 5 items
[0]
MAGEA6
[1]
−0.006
[2]
0.963
[3]
0.204
[4]
0.099
locator
section[17]/table-wrap[1]#table-5
[7] object · 16 fields
id
asset:table:pmid:30755830:6
role
table
format
jats-table
media_type
application/vnd.jats.table+json
uri
null
sha256
sha256:434897e78e3c18f0cf85ca30c08f43ff8bc04b3165ebf07c1915b764088cb9c7
bytes
629
access
open
state
verified
reader
read_table
reader_status
available
identifier
section[18]/table-wrap[1]#table-6
version
null
note
Cox regression analysis# for overall survival and disease-free survival in HCC-A patients.
structure object · 5 fields
pmcid
PMC6368834
section_index
18
section_title
Prognostic factors for overall and disease-free survival of HCC-A patients
row_count
5
column_count
7
table object · 8 fields
label
Table 6
caption
Cox regression analysis# for overall survival and disease-free survival in HCC-A patients.
rows array · 5 items
[0] array · 7 items
[0]
Survival analysis
[1]
Strata variable
[2]
Prognostic factor
[3]
B
[4]
SE
[5]
HR(95.0% CI)
[6]
p
[1] array · 7 items
[0]
Overall survival
[1]
None
[2]
CD5L
[3]
−0.205
[4]
0.071
[5]
0.814(0.709–0.936)
[6]
0.004**
[2] array · 6 items
[0]
Pathological stage
[1]
None
[2]
[3]
[4]
[5]
[3] array · 7 items
[0]
Disease-free survival
[1]
None
[2]
CSMD1
[3]
0.432
[4]
0.126
[5]
1.540(1.204–1.970)
[6]
0.001**
[4] array · 6 items
[0]
Pathological grade
[1]
CSMD1
[2]
0.315
[3]
0.123
[4]
1.370(1.076–1.744)
[5]
0.021*
locator
section[18]/table-wrap[1]#table-6
[8] object · 16 fields
id
asset:table:pmid:30755830:7
role
table
format
jats-table
media_type
application/vnd.jats.table+json
uri
null
sha256
sha256:46c930736d4fb73ca177f5ca6b4c26d38bc4110d5a6b6475390a130cc04fe377
bytes
1219
access
open
state
verified
reader
read_table
reader_status
available
identifier
section[20]/table-wrap[1]#table-7
version
null
note
Expressional differences of SKGs in HCC datasets from Oncomine database.
structure object · 5 fields
pmcid
PMC6368834
section_index
20
section_title
Validation of SKGs through Oncomine database
row_count
11
column_count
7
table object · 8 fields
label
Table 7
caption
Expressional differences of SKGs in HCC datasets from Oncomine database.
rows array · 11 items
[0] array · 7 items
[0]
[1]
Cancer vs. normal
[2]
Chen liver (n = 197)
[3]
Mas liver (n = 115)
[4]
Roessler liver (n = 43)
[5]
Roessler liver 2 (n = 445)
[6]
Wurmbach liver (n = 75)
[1] array · 7 items
[0]
CD5L
[1]
Fold change p
[2]
− 7.2759.22E-19**
[3]
1.0440.605
[4]
−5.1682.51E-18**
[5]
−5.3086.52E-95**
[6]
−6.7001.23E-9**
[2] array · 7 items
[0]
IGF2
[1]
Fold change p
[2]
−3.0801.32E-5**
[3]
−1.7352.25E-4**
[4]
−3.1630.015*
[5]
−4.1543.43E-16**
[6]
−10.1202.27E-6**
[3] array · 7 items
[0]
UROC1
[1]
Fold change p
[2]
NA
[3]
NA
[4]
NA
[5]
NA
[6]
-2.1920.004**
[4] array · 7 items
[0]
SLC22A10
[1]
Fold change p
[2]
NA
[3]
NA
[4]
NA
[5]
NA
[6]
NA
[5] array · 7 items
[0]
SPP2
[1]
Fold change p
[2]
−4.9825.74E-15**
[3]
2.4827.60E-5**
[4]
−9.5813.27E-7**
[5]
−5.7901.18E-42**
[6]
−3.0860.006**
[6] array · 7 items
[0]
CSMD1
[1]
Fold change p
[2]
1.2560.011*
[3]
NA
[4]
NA
[5]
NA
[6]
1.3140.034*
[7] array · 7 items
[0]
CSAG1
[1]
Fold change p
[2]
NA
[3]
NA
[4]
NA
[5]
NA
[6]
NA
[8] array · 7 items
[0]
CSAG3
[1]
Fold change P
[2]
NA
[3]
NA
[4]
NA
[5]
NA
[6]
NA
[9] array · 7 items
[0]
MAGEA3
[1]
Fold change p
[2]
NA
[3]
1.1130.139
[4]
2.4500.011*
[5]
2.7582.53E-17**
[6]
2.8330.001**
[10] array · 7 items
[0]
MAGEA6
[1]
Fold change P
[2]
NA
[3]
1.1650.094
[4]
2.4450.009**
[5]
2.5112.16E-17**
[6]
3.2172.73E-4**
locator
section[20]/table-wrap[1]#table-7
gaps array · 2 items
[0]
asset:data:geo:GSE59259 not downloaded
[1]
asset:data:geo:GSE59259 licence not read
analysis object · 4 fields
state
partial
methods array · 4 items
[0] object · 10 fields
id
method-1
family
differential_expression
specific
limma_voom
label
Differential expression analysis
dsl_operations array · 3 items
[0]
normalise_counts
[1]
differential_expression_fit
[2]
fdr_bh
missing_operations array · 0 items
parameters object · 0 fields
data_shapes array · 1 item
[0]
count_matrix_with_condition
evidence object · 3 fields
score
1
band
verbatim
quote
The DEGs (DEGs-1) between HCC-A tumors and HCC-V tumors were identified with limma (Ritchie et al., 2015) package in R software.
[1] object · 10 fields
id
method-2
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
0.8
band
high
quote
ANOVA
[2] object · 10 fields
id
method-3
family
survival_analysis
specific
cox_proportional_hazards
label
Survival analysis
dsl_operations array · 1 item
[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
correlation_analysis
specific
spearman
label
Correlation analysis
dsl_operations array · 1 item
[0]
spearman_rho
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
Spearman correlation
targets array · 0 items
gaps array · 1 item
[0]
method.reader_differs_from_extractor
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 · 3 items
[0]
normalise_counts
[1]
differential_expression_fit
[2]
fdr_bh
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: limma_voom.
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]
GSE59259
resolved_accessions array · 1 item
[0]
GSE59259
statements array · 1 item
[0]
The following information was supplied regarding data availability: raw data were generated in the study. All the original data in this study weredownloaded from the public databases including TCGA (https://portal.gdc.cancer.gov/), GEO (https://www.ncbi.nlm.nih.gov/geo/) and Oncomine (https://www.oncomine.org/). For the SKGs identification, we used TCGA-LIHC (https://portal.gdc.cancer.gov/projects/TCGA-LIHC) and GSE59259 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=gse59259). The HCC datasets from the Oncomine database (https://www.oncomine.org) were: Chen liver, Mas liver, Roessler liver, Roessler liver 2, Wurmbach liver, Jia liver, and Iizuka Liver 2.
basis
The paper names GSE59259 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 · 3 items
[0]
normalise_counts
[1]
differential_expression_fit
[2]
fdr_bh
assets array · 9 items
[0]
source:pmid:30755830
[1]
data:geo:GSE59259
[2]
asset:table:pmid:30755830:1
[3]
asset:table:pmid:30755830:2
[4]
asset:table:pmid:30755830:3
[5]
asset:table:pmid:30755830:4
[6]
asset:table:pmid:30755830:5
[7]
asset:table:pmid:30755830:6
[8]
asset:table:pmid:30755830:7
steps array · 1 item
[0]
run_analysis
must_build object · 5 fields
dsl_operations array · 0 items
converters array · 0 items
readers array · 0 items
capabilities array · 0 items
data_gaps array · 1 item
[0]
data:geo:GSE59259
gaps array · 0 items
review object · 5 fields
state
partial
machine_critique object · 5 fields
kind
extraction_review
reader object · 5 fields
model
MiniMax-M3.1-Flash
provider
minimax
provider_family
minimax
read_at
2026-10-31T18:13:57Z
independence
single_reader
evidence_check object · 2 fields
method
verbatim
availability
verbatim
calls
3
usage object · 3 fields
prompt_tokens
53604
completion_tokens
3857
cached_tokens
792
stages array · 1 item
[0] object · 4 fields
id
extraction
state
complete
reader
MiniMax-M3.1-Flash
provider
minimax
gaps array · 3 items
[0]
review.independent_reader
[1]
review.machine_critique
[2]
review.human_critique
execution object · 5 fields
state
absent
status
not_run
mode
null
runs array · 0 items
gaps array · 1 item
[0]
execution.not_run
provenance object · 7 fields
entities array · 3 items
[0] object · 3 fields
id
pmid:30755830
type
paper
label
pmid:30755830
[1] object · 3 fields
id
source:pmid:30755830
type
manuscript
label
PMID 30755830 full text
[2] object · 3 fields
id
data:geo:GSE59259
type
dataset
label
GEO GSE59259
activities array · 3 items
[0] object · 4 fields
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activity-reading-sci-2026-11-01
type
classification
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pmid:30755830
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paper
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pmid:30755830
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source:pmid:30755830
type
manuscript
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PMID 30755830 full text
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data:geo:GSE59259
type
dataset
label
GEO GSE59259
agent
agent:corpus-assay-engine
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activity-read-30755830
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extraction
used array · 1 item
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source:pmid:30755830
agent
agent:minimax-reader
[2] object · 4 fields
id
activity-resolve-GSE59259
type
accession_resolution
used array · 1 item
[0]
data:geo:GSE59259
agent
agent:corpus-assay-engine
agents array · 2 items
[0] object · 3 fields
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agent:corpus-assay-engine
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software
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Corpus assay engine
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agent:minimax-reader
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source_run_id
reading-sci-2026-11-01
dsl_catalogue_fingerprint
343fb30756ba6ec3
capability_table_fingerprint
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ba34b49490d9bfaf
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parent_id
pmid:30755830
parent_hash
sha256:3cbb0a7faa6852dfc999e6488b94041800a8f44d9863156fc6a28a83ceabc0d6
fork_of
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asset:data:geo:GSE59259 licence not read
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execution.not_run
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method.reader_differs_from_extractor
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review.human_critique
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role
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f2132e96ae6c7a4e
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normalise_counts
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differential_expression_fit
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fdr_bh
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dsl_catalogue
f2132e96ae6c7a4e
evidence array · 1 item
[0]
The DEGs (DEGs-1) between HCC-A tumors and HCC-V tumors were identified with limma (Ritchie et al., 2015) package in R software.
order_basis
analysis_only
id
assay:1
Complete file
{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:30755830", "kind": "science-record", "revision": 8, "content_hash": "sha256:86ec1ea3a35dc7fc3188ddc7f2ead76c5f23fa75336c99f031140cb49127d9e7", "created_at": "2026-11-01T15:40:42Z", "updated_at": "2026-11-01T22:43:48Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification of special key genes for alcohol-related hepatocellular carcinoma through bioinformatic analysis.", "doi": "10.7717/peerj.6375", "pmid": "30755830", "authors": ["Xiuzhi Zhang", "Chunyan Kang", "Ningning Li", "Xiaoli Liu", "Jinzhong Zhang", "Fenglan Gao", "Liping Dai"], "journal": "PeerJ", "year": 2019, "abstract": "BACKGROUND: Alcohol-related hepatocellular carcinoma (HCC) was reported to be diagnosed at a later stage, but the mechanism was unknown. This study aimed to identify special key genes (SKGs) during alcohol-related HCC development and progression.\nMETHODS: The mRNA data of 369 HCC patients and the clinical information were downloaded from the Cancer Genome Atlas project (TCGA). The 310 patients with certain HCC-related risk factors were included for analysis and divided into seven groups according to the risk factors. Survival analyses were applied for the HCC patients of different groups. The patients with hepatitis B virus or hepatitis C virus infection only were combined into the HCC-V group for further analysis. The differentially expressed genes (DEGs) between the HCCs with alcohol consumption only (HCC-A) and HCC-V tumors were identified through limma package in R with cutoff criteria│log2 fold change (logFC)|>1.0 and p < 0.05. The DEGs between eight alcohol-related HCCs and their paired normal livers of GSE59259 from the Gene Expression Omnibus (GEO) were identified through GEO2R (a built-in tool in GEO database) with cutoff criteria |logFC|> 2.0 and adj.p < 0.05. The intersection of the two sets of DEGs was considered SKGs which were then investigated for their specificity through comparisons between HCC-A and other four HCC groups. The SKGs were analyzed for their correlations with HCC-A stage and grade and their prognostic power for HCC-A patients. The expressional differences of the SKGs in the HCCs in whole were also investigated through Gene Expression Profiling Interactive Analysis (GEPIA). The SKGs in HCC were validated through Oncomine database analysis.\nRESULTS: Pathological stage is an independent prognostic factor for HCC patients. HCC-A patients were diagnosed later than HCC patients with other risk factors. Ten SKGs were identified and nine of them were confirmed for their differences in paired samples of HCC-A patients. Three (SLC22A10, CD5L, and UROC1) and four (SLC22A10, UROC1, CSAG3, and CSMD1) confirmed genes were correlated with HCC-A stage and grade, respectively. SPP2 had a lower trend in HCC-A tumors and was negatively correlated with HCC-A stage and grade. The SKGs each was differentially expressed between HCC-A and at least one of other HCC groups. CD5L was identified to be favorable prognostic factor for overall survival while CSMD1 unfavorable prognostic factor for disease-free survival for HCC-A patients and HCC patients in whole. Through Oncomine database, the dysregulations of the SKGs in HCC and their clinical significance were confirmed.\nCONCLUSION: The poor prognosis of HCC-A patients might be due to their later diagnosis. The SKGs, especially the four stage-correlated genes (CD5L, SLC22A10, UROC1, and SPP2) might play important roles in HCC development, especially alcohol-related HCC development and progression. CD5L might be useful for overall survival and CSMD1 for disease-free survival predication in HCC, especially alcohol-related HCC.", "claims": [{"id": "claim-method", "statement": "The DEGs (DEGs-1) between HCC-A tumors and HCC-V tumors were identified with limma (Ritchie et al., 2015) package in R software.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:30755830", "locator": "sections[6] \"Identification of DEGs-1 (DEGs between HCC-A group and other HCC groups)\" paragraph 2", "quote": "The DEGs (DEGs-1) between HCC-A tumors and HCC-V tumors were identified with limma (Ritchie et al., 2015) package in R software."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The following information was supplied regarding data availability:\nraw data were generated in the study. All the original data in this study weredownloaded from the public databases including TCGA (https://portal.gdc.cancer.gov/), GEO (https://www.ncbi.nlm.nih.gov/geo/) and Oncomine (https://www.oncomine.org/).\nFor the SKGs identification, we used TCGA-LIHC (https://portal.gdc.cancer.gov/projects/TCGA-LIHC) and GSE59259 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=gse59259).\nThe HCC datasets from the Oncomine database (https://www.oncomine.org) were: Chen liver, Mas liver, Roessler liver, Roessler liver 2, Wurmbach liver, Jia liver, and Iizuka Liver 2.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:30755830", "locator": "sections[33] \"Data Availability Statement\" paragraphs 1-5", "quote": "The following information was supplied regarding data availability:\nraw data were generated in the study. All the original data in this study weredownloaded from the public databases including TCGA (https://portal.gdc.cancer.gov/), GEO (https://www.ncbi.nlm.nih.gov/geo/) and Oncomine (https://www.oncomine.org/).\nFor the SKGs identification, we used TCGA-LIHC (https://portal.gdc.cancer.gov/projects/TCGA-LIHC) and GSE59259 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=gse59259).\nThe HCC datasets from the Oncomine database (https://www.oncomine.org) were: Chen liver, Mas liver, Roessler liver, Roessler liver 2, Wurmbach liver, Jia liver, and Iizuka Liver 2."}], "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:30755830"], "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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The physical bench the paper used is not, so a physical validation cannot be run here."}, "data": {"tier": "R1", "reachable": true, "accessions": ["GSE59259"], "resolved_accessions": ["GSE59259"], "statements": ["The following information was supplied regarding data availability:\nraw data were generated in the study. All the original data in this study weredownloaded from the public databases including TCGA (https://portal.gdc.cancer.gov/), GEO (https://www.ncbi.nlm.nih.gov/geo/) and Oncomine (https://www.oncomine.org/).\nFor the SKGs identification, we used TCGA-LIHC (https://portal.gdc.cancer.gov/projects/TCGA-LIHC) and GSE59259 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=gse59259).\nThe HCC datasets from the Oncomine database (https://www.oncomine.org) were: Chen liver, Mas liver, Roessler liver, Roessler liver 2, Wurmbach liver, Jia liver, and Iizuka Liver 2."], "basis": "The paper names GSE59259 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:30755830", "data:geo:GSE59259", "asset:table:pmid:30755830:1", "asset:table:pmid:30755830:2", "asset:table:pmid:30755830:3", "asset:table:pmid:30755830:4", "asset:table:pmid:30755830:5", "asset:table:pmid:30755830:6", "asset:table:pmid:30755830:7"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE59259"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-10-31T18:13:57Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 3, "usage": {"prompt_tokens": 53604, "completion_tokens": 3857, "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:30755830", "type": "paper", "label": "pmid:30755830"}, {"id": "source:pmid:30755830", "type": "manuscript", "label": "PMID 30755830 full text"}, {"id": "data:geo:GSE59259", "type": "dataset", "label": "GEO GSE59259"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:30755830", "type": "paper", "label": "pmid:30755830"}, {"id": "source:pmid:30755830", "type": "manuscript", "label": "PMID 30755830 full text"}, {"id": "data:geo:GSE59259", "type": "dataset", "label": "GEO GSE59259"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-30755830", "type": "extraction", "used": ["source:pmid:30755830"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE59259", "type": "accession_resolution", "used": ["data:geo:GSE59259"], "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:30755830", "parent_hash": "sha256:3cbb0a7faa6852dfc999e6488b94041800a8f44d9863156fc6a28a83ceabc0d6", "fork_of": null, "generation": 7}, "gaps": ["asset:data:geo:GSE59259 licence not read", "asset:data:geo:GSE59259 not downloaded", "execution.not_run", "method.reader_differs_from_extractor", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"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": ["The DEGs (DEGs-1) between HCC-A tumors and HCC-V tumors were identified with limma (Ritchie et al., 2015) package in R software."], "order_basis": "analysis_only", "id": "assay:1"}]}