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pmid:39072180
Integrated single-cell and bulk RNA sequencing revealed an epigenetic signature predicts prognosis and tumor microenvironment colorectal cancer heterogeneity.
Han-Xuan Liu · Jie Feng · Jing-Jing Jiang · Wan-Jun Shen · Yu Zheng · Gang Liu · Xiang-Yang Gao
World journal of gastrointestinal oncology · 2024 doi:10.4251/wjgo.v16.i7.3032
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Complete file
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Epigenetic regulation has been widely reported for its role in cancer development.\nAIM: To construct a robust prognostic signature, we used developed and validated across datasets.\nMETHODS: After constructing the signature, the prognostic value of the signature was evaluated in the TCGA cohort and six independent datasets (GSE17526, GSE17537, GSE33113, GSE37892, GSE39048 and GSE39582). The clinical, genomic and transcriptomic features related to the signature were identified. The correlations of the signature score with immune cell infiltration and cell-cell interactions were analyzed. The correlations between the signature score and the sensitivity to different drugs were also predicted.\nRESULTS: In the TCGA cohort, patients in the low-risk group according to the signature score had longer survival than those in the high-risk group, and this finding was validated in the validation datasets. The signature was a prognostic factor independent of age and sex and was correlated with stage and PD-1/PD-L1 expression. Area under the receiving operating characteristic curve was 0.72. Genomic association analyses revealed that samples from high-risk patients exhibited chromosomal instability. Transcriptomic analyses revealed that the signature score was significantly associated with multiple cellular pathways. Bulk RNA-seq and single-cell sequencing data revealed that the signature reflected differences in infiltrating immune cell-tumor cell interactions, especially for macrophages. The signature also predicted the putative drug sensitivity of CRC samples.\nCONCLUSION: The signature is a valuable biomarker for predicting CRC prognosis and reflects multiple features of CRC, especially macrophage infiltration in the microenvironment.", "claims": [{"id": "claim-method", "statement": "Cox univariate regression was used to correlate the expression of these genes with overall survival.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:39072180", "locator": "sections[5] \"Candidate gene selection, signature development and validation\" paragraph 2", "quote": "Cox univariate regression was used to correlate the expression of these genes with overall survival."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Data on gene expression, clinical features, mutations, gene copy number and DNA methylation for the TCGA-CRC cohort were retrieved from the cBioPortal[17] database.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:39072180", "locator": "sections[4] \"Data collection and patient enrollment\" paragraph 2", "quote": "Data on gene expression, clinical features, mutations, gene copy number and DNA methylation for the TCGA-CRC cohort were retrieved from the cBioPortal[17] database."}], "state": "complete"}, {"id": "claim-target-result", "statement": "A 10-gene prognostic signature stratified colorectal cancer patients by survival, with low-risk patients showing longer survival than high-risk patients in the TCGA cohort and independent validation datasets.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:39072180", "locator": "sections[0] \"Abstract\" paragraph 4", "quote": "In the TCGA cohort, patients in the low-risk group according to the signature score had longer survival than those in the high-risk group, and this finding was validated in the validation datasets."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "A 10-gene prognostic signature stratified colorectal cancer patients by survival, with low-risk patients showing longer survival than high-risk patients in the TCGA cohort and independent validation datasets.", "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:39072180"], "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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Bulk RNA-seq and single-cell sequencing data revealed tha", "048 and GSE39582). The clinical, genomic and transcriptomic features related to the signature were ident", "patients exhibited chromosomal instability. Transcriptomic analyses revealed that the signature score w"], "order_basis": "paper_text_order:0", "id": "assay:1"}, {"role": "analysis", "definition_id": "survival_analysis", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["cox_ph"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["Cox univariate regression was used to correlate the expression of these genes with overall survival."], "order_basis": "consumes_earlier_output", "id": "assay:2"}]}