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pmid:32849853

Identification of a Five-Gene Signature for Predicting Survival in Malignant Pleural Mesothelioma Patients.

Yiyang Bai · Xiao Wang · Jia Hou · Luying Geng · Xuan Liang · Zhiping Ruan · Hui Guo · Kejun Nan · Lili Jiang

Frontiers in genetics · 2020 doi:10.3389/fgene.2020.00899

Paper

complete

Experiment

complete

Data

partial

Analysis

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Execution

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Record details sci_version · id · kind · revision · content_hash · schema · created_at · updated_at · generator
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pmid:32849853
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2026-11-01T15:41:08Z
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title
Identification of a Five-Gene Signature for Predicting Survival in Malignant Pleural Mesothelioma Patients.
doi
10.3389/fgene.2020.00899
pmid
32849853
authors array · 9 items
[0]
Yiyang Bai
[1]
Xiao Wang
[2]
Jia Hou
[3]
Luying Geng
[4]
Xuan Liang
[5]
Zhiping Ruan
[6]
Hui Guo
[7]
Kejun Nan
[8]
Lili Jiang
journal
Frontiers in genetics
year
2020
abstract
Malignant pleural mesothelioma (MPM), predominantly caused by asbestos exposure, is a highly aggressive cancer with poor prognosis. The staging systems currently used in clinics is inadequate in evaluating the prognosis of MPM. In this study, a five-gene signature was developed and enrolled into a prognostic risk score model by LASSO Cox regression analysis based on two expression profiling datasets (GSE2549 and GSE51024) from Gene Expression Omnibus (GEO). The five-gene signature was further validated using the Cancer Genome Atlas (TCGA) MPM dataset. Univariate and multivariate Cox analyses proved that the five-gene signature was an independent prognostic factor for MPM. The signature remained statistically significant upon stratification by Brigham stage, AJCC stage, gender, tumor size, and lymph node status. Time-dependent receiver operating characteristic (ROC) curve indicated good performance of our model in predicting 1- and 2-years overall survival in MPM patients. The C-index was 0.784 for GSE2549 and 0.753 for the TCGA dataset showing moderate predictive accuracy of our model. Furthermore, Gene Set Enrichment Analysis suggested that the five-gene signature was related to pathways resulting in MPM tumor progression. Together, we have established a five-gene signature significantly associated with prognosis in MPM patients. Hence, the five-genes signature may serve as a potentially useful prognostic tool for MPM patients.
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To identify the differentially expressed genes (DEGs), GSE2549 and GSE51024 MPM datasets were employed. After annotating the probes into gene symbols by the platform annotation files, we used R package LIMMA (Ritchie et al., 2015) to get the DEGs between the tumor and normal tissue following the criteria of adjusted P-value < 0.05, |log2FoldChange| > 1 in both sets.
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sections[4] "Differential mRNA Analysis" paragraph 2
quote
To identify the differentially expressed genes (DEGs), GSE2549 and GSE51024 MPM datasets were employed. After annotating the probes into gene symbols by the platform annotation files, we used R package LIMMA (Ritchie et al., 2015) to get the DEGs between the tumor and normal tissue following the criteria of adjusted P-value < 0.05, |log2FoldChange| > 1 in both sets.
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Publicly available datasets were analyzed in this study. This data can be found here: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE2549, https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE51024, and https://www.cancer.gov/about-nci/organization/ccg/research/structural-genomics/tcga.
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sections[17] "Data Availability Statement" paragraph 2
quote
Publicly available datasets were analyzed in this study. This data can be found here: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE2549, https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE51024, and https://www.cancer.gov/about-nci/organization/ccg/research/structural-genomics/tcga.
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Gene Expression of Malignant Pleural Mesothelioma Tumor and paired Normal Lung tissue
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Construction and Validation of the Prognostic Risk Score Model for MPM
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12
section_title
Stratified Survival Analysis of the Five-Gene Risk Score Model
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10
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5
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TABLE 3
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Stratified survival analysis of GSE2549.
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[0] array · 5 items
[0]
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[1]
Low risk
[2]
High risk
[3]
P-value
[4]
HR (95% CI)
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Histological subtype
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[2]
[3]
[4]
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Epithelial
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15
[2]
8
[3]
0.0006
[4]
4.444(1.254−15.75)
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11
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0.5396
[4]
1.390(0.4759−4.058)
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N stage
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[2]
[3]
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6
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2
[3]
0.0473
[4]
5.486(0.3636−82.78)
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[0]
N +
[1]
14
[2]
17
[3]
0.001
[4]
3.242(1.465−7.171)
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[0]
Brigham stage
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[2]
[3]
[4]
[8] array · 5 items
[0]
I + II
[1]
6
[2]
6
[3]
0.0138
[4]
4.529(1.098−18.69)
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[0]
III + IV
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14
[2]
13
[3]
0.0012
[4]
3.485(1.391−8.727)
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section[12]/table-wrap[1]#T3
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Stratified survival analysis of TCGA.
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PMC7427512
section_index
12
section_title
Stratified Survival Analysis of the Five-Gene Risk Score Model
row_count
13
column_count
5
table object · 8 fields
label
TABLE 4
caption
Stratified survival analysis of TCGA.
rows array · 13 items
[0] array · 5 items
[0]
Variable
[1]
Low-risk
[2]
High-risk
[3]
P-value
[4]
HR (95% CI)
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[0]
Gender
[1]
[2]
[3]
[4]
[2] array · 5 items
[0]
Female
[1]
5
[2]
6
[3]
0.0123
[4]
3.806 (0.961–15.08)
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[0]
Male
[1]
21
[2]
24
[3]
0.0001
[4]
3.110 (1.559–6.204)
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[0]
AJCC stage
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[2]
[3]
[4]
[5] array · 5 items
[0]
I + II
[1]
6
[2]
12
[3]
0.0322
[4]
2.534 (0.967–6.640)
[6] array · 5 items
[0]
III + IV
[1]
20
[2]
18
[3]
0.0006
[4]
3.174 (1.444–6.973)
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[0]
T stage
[1]
[2]
[3]
[4]
[8] array · 5 items
[0]
T1 + T2
[1]
12
[2]
16
[3]
0.0018
[4]
2.889 (1.268–6.582)
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[0]
T3 + T4
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14
[2]
14
[3]
0.0025
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N stage
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[3]
[4]
[11] array · 5 items
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N0
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12
[2]
21
[3]
0.0017
[4]
2.823 (1.372–5.806)
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N +
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14
[2]
9
[3]
0.0013
[4]
3.937 (1.163–13.33)
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section[13]/table-wrap[1]#T5
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C-index comparison in GSE2549 dataset.
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pmcid
PMC7427512
section_index
13
section_title
Comparison of Five-Gene Risk Model With Other Clinicopathological Factors and Literature Models
row_count
3
column_count
4
table object · 8 fields
label
TABLE 5
caption
C-index comparison in GSE2549 dataset.
rows array · 3 items
[0] array · 4 items
[0]
Signature
[1]
C-index
[2]
Z-score
[3]
P-value
[1] array · 4 items
[0]
Our five-gene signature
[1]
0.784 (95% CI = 0.674–0.894)
[2]
−0.35839
[3]
0.720051
[2] array · 4 items
[0]
Three-gene signature by Zhou et al. (2019)
[1]
0.770 (95% CI = 0.725–0.815)
[2]
[3]
locator
section[13]/table-wrap[1]#T5
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asset:table:pmid:32849853:6
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section[13]/table-wrap[2]#T6
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C-index comparison in TCGA dataset.
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pmcid
PMC7427512
section_index
13
section_title
Comparison of Five-Gene Risk Model With Other Clinicopathological Factors and Literature Models
row_count
3
column_count
4
table object · 8 fields
label
TABLE 6
caption
C-index comparison in TCGA dataset.
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[0] array · 4 items
[0]
Signature
[1]
C-index
[2]
Z-score
[3]
P-value
[1] array · 4 items
[0]
Our five-gene signature
[1]
0.753 (95% CI = 0.698–0.808)
[2]
−3.41016
[3]
0.000649
[2] array · 4 items
[0]
Three-gene signature by Zhou et al. (2019)
[1]
0.608 (95% CI = 0.567–0.649)
[2]
[3]
locator
section[13]/table-wrap[2]#T6
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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
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quote
To identify the differentially expressed genes (DEGs), GSE2549 and GSE51024 MPM datasets were employed. After annotating the probes into gene symbols by the platform annotation files, we used R package LIMMA (Ritchie et al., 2015) to get the DEGs between the tumor and normal tissue following the criteria of adjusted P-value < 0.05, |log2FoldChange| > 1 in both sets.
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Survival analysis
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time_to_event_with_censoring
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Kaplan-Meier
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Survival analysis
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time_to_event_with_censoring
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Cox regression
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method-4
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survival_analysis
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Survival analysis
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logrank_test
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time_to_event_with_censoring
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0.8
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method.reader_differs_from_extractor
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complete
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capability:computational_analysis
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meta_analysis
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Automated Assays Laravel application and simulated adapters
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capability:computational_analysis
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The computational analysis is owned. The physical bench the paper used is not, so a physical validation cannot be run here.
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GSE2549
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GSE51024
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GSE2549
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GSE51024
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Publicly available datasets were analyzed in this study. This data can be found here: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE2549, https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE51024, and https://www.cancer.gov/about-nci/organization/ccg/research/structural-genomics/tcga.
basis
The paper names GSE2549, GSE51024 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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To identify the differentially expressed genes (DEGs), GSE2549 and GSE51024 MPM datasets were employed. After annotating the probes into gene symbols by the platform annotation files, we used R package LIMMA (Ritchie et al., 2015) to get the DEGs between the tumor and normal tissue following the criteria of adjusted P-value < 0.05, |log2FoldChange| > 1 in both sets.
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{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:32849853", "kind": "science-record", "revision": 8, "content_hash": "sha256:5ba4a41a00d3627a9960ca3f564d4f78693967dc94ba1d6139c64d057ae69dfb", "created_at": "2026-11-01T15:41:08Z", "updated_at": "2026-11-01T22:45:15Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification of a Five-Gene Signature for Predicting Survival in Malignant Pleural Mesothelioma Patients.", "doi": "10.3389/fgene.2020.00899", "pmid": "32849853", "authors": ["Yiyang Bai", "Xiao Wang", "Jia Hou", "Luying Geng", "Xuan Liang", "Zhiping Ruan", "Hui Guo", "Kejun Nan", "Lili Jiang"], "journal": "Frontiers in genetics", "year": 2020, "abstract": "Malignant pleural mesothelioma (MPM), predominantly caused by asbestos exposure, is a highly aggressive cancer with poor prognosis. The staging systems currently used in clinics is inadequate in evaluating the prognosis of MPM. In this study, a five-gene signature was developed and enrolled into a prognostic risk score model by LASSO Cox regression analysis based on two expression profiling datasets (GSE2549 and GSE51024) from Gene Expression Omnibus (GEO). The five-gene signature was further validated using the Cancer Genome Atlas (TCGA) MPM dataset. Univariate and multivariate Cox analyses proved that the five-gene signature was an independent prognostic factor for MPM. The signature remained statistically significant upon stratification by Brigham stage, AJCC stage, gender, tumor size, and lymph node status. Time-dependent receiver operating characteristic (ROC) curve indicated good performance of our model in predicting 1- and 2-years overall survival in MPM patients. The C-index was 0.784 for GSE2549 and 0.753 for the TCGA dataset showing moderate predictive accuracy of our model. Furthermore, Gene Set Enrichment Analysis suggested that the five-gene signature was related to pathways resulting in MPM tumor progression. Together, we have established a five-gene signature significantly associated with prognosis in MPM patients. Hence, the five-genes signature may serve as a potentially useful prognostic tool for MPM patients.", "claims": [{"id": "claim-method", "statement": "To identify the differentially expressed genes (DEGs), GSE2549 and GSE51024 MPM datasets were employed. 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After annotating the probes into gene symbols by the platform annotation files, we used R package LIMMA (Ritchie et al., 2015) to get the DEGs between the tumor and normal tissue following the criteria of adjusted P-value < 0.05, |log2FoldChange| > 1 in both sets."}}, {"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": 0.7, "band": "medium", "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": ["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: limma_voom."}, "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": ["GSE2549", "GSE51024"], "resolved_accessions": ["GSE2549", "GSE51024"], "statements": ["Publicly available datasets were analyzed in this study. This data can be found here: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE2549, https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE51024, and https://www.cancer.gov/about-nci/organization/ccg/research/structural-genomics/tcga."], "basis": "The paper names GSE2549, GSE51024 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:32849853", "data:geo:GSE2549", "asset:table:pmid:32849853:1", "asset:table:pmid:32849853:2", "asset:table:pmid:32849853:3", "asset:table:pmid:32849853:4", "asset:table:pmid:32849853:5", "asset:table:pmid:32849853:6"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE2549"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-10-31T18:22:11Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 3, "usage": {"prompt_tokens": 29042, "completion_tokens": 2261, "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:32849853", "type": "paper", "label": "pmid:32849853"}, {"id": "source:pmid:32849853", "type": "manuscript", "label": "PMID 32849853 full text"}, {"id": "data:geo:GSE2549", "type": "dataset", "label": "GEO GSE2549"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:32849853", "type": "paper", "label": "pmid:32849853"}, {"id": "source:pmid:32849853", "type": "manuscript", "label": "PMID 32849853 full text"}, {"id": "data:geo:GSE2549", "type": "dataset", "label": "GEO GSE2549"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-32849853", "type": "extraction", "used": ["source:pmid:32849853"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE2549", "type": "accession_resolution", "used": ["data:geo:GSE2549"], "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:32849853", "parent_hash": "sha256:9b511d5d085532be1076aac4d3ca60648ed3991efdcc639b188eb45f06da0b0d", "fork_of": null, "generation": 7}, "gaps": ["asset:data:geo:GSE2549 licence not read", "asset:data:geo:GSE2549 not downloaded", "asset:data:geo:GSE51024 licence not read", "asset:data:geo:GSE51024 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": ["To identify the differentially expressed genes (DEGs), GSE2549 and GSE51024 MPM datasets were employed. After annotating the probes into gene symbols by the platform annotation files, we used R package LIMMA (Ritchie et al., 2015) to get the DEGs between the tumor and normal tissue following the criteria of adjusted P-value < 0.05, |log2FoldChange| > 1 in both sets."], "order_basis": "analysis_only", "id": "assay:1"}]}