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pmid:35281839

Exploring Immune-Related Prognostic Signatures in the Tumor Microenvironment of Colon Cancer.

Lichao Cao · Tong Li · Ying Ba · Erfei Chen · Jin Yang · Hezi Zhang

Frontiers in genetics · 2022 doi:10.3389/fgene.2022.801484

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title
Exploring Immune-Related Prognostic Signatures in the Tumor Microenvironment of Colon Cancer.
doi
10.3389/fgene.2022.801484
pmid
35281839
authors array · 6 items
[0]
Lichao Cao
[1]
Tong Li
[2]
Ying Ba
[3]
Erfei Chen
[4]
Jin Yang
[5]
Hezi Zhang
journal
Frontiers in genetics
year
2022
abstract
Background: Colon cancer is a common malignant tumor with poor prognosis. The aim of this study is to explore the immune-related prognostic signatures and the tumor immune microenvironment of colon cancer. Methods: The mRNA expression data of TCGA-COAD from the UCSC Xena platform and the list of immune-related genes (IRGs) from the ImmPort database were used to identify immune-related differentially expressed genes (DEGs). Then, we constructed an immune-related risk score prognostic model and validated its predictive performance in the test dataset, the whole dataset, and two independent GEO datasets. In addition, we explored the differences in tumor-infiltrating immune cell types, tumor mutation burden (TMB), microsatellite status, and expression levels of immune checkpoints and their ligands between the high-risk and low-risk score groups. Moreover, the potential value of the identified immune-related signature with respect to immunotherapy was investigated based on an immunotherapeutic cohort (Imvigor210) treated with an anti-PD-L1 agent. Results: Seven immune-related DEGs were identified as prognostic signatures. The areas under the curves (AUCs) of the constructed risk score model for overall survival (OS) were calculated (training dataset: 0.780 at 3 years, 0.801 at 4 years, and 0.766 at 5 years; test dataset: 0.642 at 3 years, 0.647 at 4 years, and 0.629 at 5 years; and the whole dataset: 0.642 at 3 years, 0.647 at 4 years, and 0.629 at 5 years). In the high-risk score group of the whole dataset, patients had worse OS, higher TMN stages, advanced pathological stages, and a higher TP53 mutation rate (p < 0.05). In addition, a high level of resting NK cells or M0 macrophages, and high TMB were significantly related to poor OS (p < 0.05). Also, we observed that high-risk score patients had a high expression level of PD-L1, PD-1, and CTLA-4 (p < 0.05). The patients with high-risk scores demonstrated worse prognosis than those with low-risk scores in multiple datasets (GSE39582: p = 0.0023; GSE17536: p = 0.0008; immunotherapeutic cohort without platinum treatment: p = 0.0014; immunotherapeutic cohort with platinum treatment: p = 0.0027). Conclusion: We developed a robust immune-related prognostic signature that performed great in multiple cohorts and explored the characteristics of the tumor immune microenvironment of colon cancer patients, which may give suggestions for the prognosis and immunotherapy in the future.
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First, we identified the candidate prognostic signature using the univariable Cox proportional hazards regression model and Survival R package. To avoid over-fitting, all genes with p-value < 0.05 were involved in the subsequent least absolute shrinkage and selection operator (LASSO) analysis using the glmnet R package.
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sections[8] "Construction and Validation of the Immune-Related Prognostic Model for Colon Cancer" paragraph 2
quote
First, we identified the candidate prognostic signature using the univariable Cox proportional hazards regression model and Survival R package. To avoid over-fitting, all genes with p-value < 0.05 were involved in the subsequent least absolute shrinkage and selection operator (LASSO) analysis using the glmnet R package.
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The mRNA sequencing data, mutation profiling data, and clinical information were downloaded from the UCSC Xena platform (https://xenabrowser.net/datapages/).
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sections[4] "TCGA Cohorts and the List of Immune-Related Genes" paragraph 2
quote
The mRNA sequencing data, mutation profiling data, and clinical information were downloaded from the UCSC Xena platform (https://xenabrowser.net/datapages/).
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The seven-gene immune-related risk score had time-dependent OS AUCs of 0.780, 0.801, and 0.766 at 3, 4, and 5 years in the training dataset, respectively.
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sections[0] "Abstract" paragraph 3
quote
The areas under the curves (AUCs) of the constructed risk score model for overall survival (OS) were calculated (training dataset: 0.780 at 3 years, 0.801 at 4 years, and 0.766 at 5 years; test dataset: 0.642 at 3 years, 0.647 at 4 years, and 0.629 at 5 years; and the whole dataset: 0.642 at 3 years, 0.647 at 4 years, and 0.629 at 5 years).
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The seven-gene immune-related risk score had time-dependent OS AUCs of 0.780, 0.801, and 0.766 at 3, 4, and 5 years in the training dataset, respectively.
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Metastasis Gene Expression Profile Predicts Recurrence and Death in Colon Cancer Patients (Moffitt Samples)
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sample_count
585
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570
taxon
Homo sapiens
title
Gene expression Classification of Colon Cancer defines six molecular subtypes with distinct clinical, molecular and survival characteristics [Expression]
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2026-11-01T15:39:54Z
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[2]
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[3]
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partial
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time_to_event_with_censoring
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quote
First, we identified the candidate prognostic signature using the univariable Cox proportional hazards regression model and Survival R package. To avoid over-fitting, all genes with p-value < 0.05 were involved in the subsequent least absolute shrinkage and selection operator (LASSO) analysis using the glmnet R package.
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false
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complete
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[8]
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candidate
Automated Assays Laravel application and simulated adapters
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complete
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nothing:replicable_now
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method object · 5 fields
tier
R1
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cox_ph
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basis
The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: cox_proportional_hazards.
capability object · 4 fields
tier
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tier
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[0]
The mRNA sequencing data, mutation profiling data, and clinical information were downloaded from the UCSC Xena platform (https://xenabrowser.net/datapages/).
basis
The paper names GSE39582, GSE17536 in GEO database and the accession resolves in the repository. No dataset was downloaded and no licence was read.
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[0]
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[1]
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[0]
data:geo:GSE17536
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extraction_review
reader object · 5 fields
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minimax
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minimax
read_at
2026-11-01T17:37:51Z
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single_reader
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PMID 35281839 full text
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data:geo:GSE17536
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GEO GSE17536
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source:pmid:35281839
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PMID 35281839 full text
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GEO GSE17536
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[2]
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[3]
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[4]
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[5]
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[6]
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f2132e96ae6c7a4e
evidence array · 1 item
[0]
First, we identified the candidate prognostic signature using the univariable Cox proportional hazards regression model and Survival R package. To avoid over-fitting, all genes with p-value < 0.05 were involved in the subsequent least absolute shrinkage and selection operator (LASSO) analysis using the glmnet R package.
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Complete file
{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:35281839", "kind": "science-record", "revision": 5, "content_hash": "sha256:0568fc7ef1076dc720eca8a8676e51768dd509ad5b60a0bd478858c1ce6d102a", "created_at": "2026-11-01T18:14:03Z", "updated_at": "2026-11-01T22:48:39Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Exploring Immune-Related Prognostic Signatures in the Tumor Microenvironment of Colon Cancer.", "doi": "10.3389/fgene.2022.801484", "pmid": "35281839", "authors": ["Lichao Cao", "Tong Li", "Ying Ba", "Erfei Chen", "Jin Yang", "Hezi Zhang"], "journal": "Frontiers in genetics", "year": 2022, "abstract": "Background: Colon cancer is a common malignant tumor with poor prognosis. The aim of this study is to explore the immune-related prognostic signatures and the tumor immune microenvironment of colon cancer. Methods: The mRNA expression data of TCGA-COAD from the UCSC Xena platform and the list of immune-related genes (IRGs) from the ImmPort database were used to identify immune-related differentially expressed genes (DEGs). Then, we constructed an immune-related risk score prognostic model and validated its predictive performance in the test dataset, the whole dataset, and two independent GEO datasets. In addition, we explored the differences in tumor-infiltrating immune cell types, tumor mutation burden (TMB), microsatellite status, and expression levels of immune checkpoints and their ligands between the high-risk and low-risk score groups. Moreover, the potential value of the identified immune-related signature with respect to immunotherapy was investigated based on an immunotherapeutic cohort (Imvigor210) treated with an anti-PD-L1 agent. Results: Seven immune-related DEGs were identified as prognostic signatures. The areas under the curves (AUCs) of the constructed risk score model for overall survival (OS) were calculated (training dataset: 0.780 at 3 years, 0.801 at 4 years, and 0.766 at 5 years; test dataset: 0.642 at 3 years, 0.647 at 4 years, and 0.629 at 5 years; and the whole dataset: 0.642 at 3 years, 0.647 at 4 years, and 0.629 at 5 years). In the high-risk score group of the whole dataset, patients had worse OS, higher TMN stages, advanced pathological stages, and a higher TP53 mutation rate (p < 0.05). In addition, a high level of resting NK cells or M0 macrophages, and high TMB were significantly related to poor OS (p < 0.05). Also, we observed that high-risk score patients had a high expression level of PD-L1, PD-1, and CTLA-4 (p < 0.05). The patients with high-risk scores demonstrated worse prognosis than those with low-risk scores in multiple datasets (GSE39582: p = 0.0023; GSE17536: p = 0.0008; immunotherapeutic cohort without platinum treatment: p = 0.0014; immunotherapeutic cohort with platinum treatment: p = 0.0027). Conclusion: We developed a robust immune-related prognostic signature that performed great in multiple cohorts and explored the characteristics of the tumor immune microenvironment of colon cancer patients, which may give suggestions for the prognosis and immunotherapy in the future.", "claims": [{"id": "claim-method", "statement": "First, we identified the candidate prognostic signature using the univariable Cox proportional hazards regression model and Survival R package. To avoid over-fitting, all genes with p-value < 0.05 were involved in the subsequent least absolute shrinkage and selection operator (LASSO) analysis using the glmnet R package.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35281839", "locator": "sections[8] \"Construction and Validation of the Immune-Related Prognostic Model for Colon Cancer\" paragraph 2", "quote": "First, we identified the candidate prognostic signature using the univariable Cox proportional hazards regression model and Survival R package. To avoid over-fitting, all genes with p-value < 0.05 were involved in the subsequent least absolute shrinkage and selection operator (LASSO) analysis using the glmnet R package."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The mRNA sequencing data, mutation profiling data, and clinical information were downloaded from the UCSC Xena platform (https://xenabrowser.net/datapages/).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35281839", "locator": "sections[4] \"TCGA Cohorts and the List of Immune-Related Genes\" paragraph 2", "quote": "The mRNA sequencing data, mutation profiling data, and clinical information were downloaded from the UCSC Xena platform (https://xenabrowser.net/datapages/)."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The seven-gene immune-related risk score had time-dependent OS AUCs of 0.780, 0.801, and 0.766 at 3, 4, and 5 years in the training dataset, respectively.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:35281839", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "The areas under the curves (AUCs) of the constructed risk score model for overall survival (OS) were calculated (training dataset: 0.780 at 3 years, 0.801 at 4 years, and 0.766 at 5 years; test dataset: 0.642 at 3 years, 0.647 at 4 years, and 0.629 at 5 years; and the whole dataset: 0.642 at 3 years, 0.647 at 4 years, and 0.629 at 5 years)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The seven-gene immune-related risk score had time-dependent OS AUCs of 0.780, 0.801, and 0.766 at 3, 4, and 5 years in the training dataset, respectively.", "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:35281839"], "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. This lane did not download the dataset or read its licence.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE17536"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "complete", "blocked_on": null, "description": "Apply the paper's statistical method to the resolved series and compare the result with the published target.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE17536"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:35281839", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fgene.2022.801484", "sha256": 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To avoid over-fitting, all genes with p-value < 0.05 were involved in the subsequent least absolute shrinkage and selection operator (LASSO) analysis using the glmnet R package."}}, {"id": "method-2", "family": "group_comparison", "specific": "wilcoxon", "label": "Group comparison", "dsl_operations": [], "missing_operations": ["group_comparison_wilcoxon"], "expressible": false, "parameters": {}, "data_shapes": ["two_or_more_groups_continuous"], "evidence": {"score": 0.8, "band": "high", "quote": "Wilcoxon"}}], "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": ["cox_ph"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: cox_proportional_hazards."}, "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": ["GSE39582", "GSE17536"], "resolved_accessions": ["GSE39582", "GSE17536"], "statements": ["The mRNA sequencing data, mutation profiling data, and clinical information were downloaded from the UCSC Xena platform (https://xenabrowser.net/datapages/)."], "basis": "The paper names GSE39582, GSE17536 in GEO database and the accession resolves in the repository. 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To avoid over-fitting, all genes with p-value < 0.05 were involved in the subsequent least absolute shrinkage and selection operator (LASSO) analysis using the glmnet R package."], "order_basis": "analysis_only", "id": "assay:1"}]}