Five EMT-related genes signature predicts overall survival and immune environment in microsatellite instability-high gastric cancer.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:35789544", "kind": "science-record", "revision": 3, "content_hash": "sha256:802e0c17cf2cb6c6ded7810cedb683c931bca82726d42d29cdd5c4e58df2a654", "created_at": "2026-11-01T18:14:49Z", "updated_at": "2026-11-01T21:28:17Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Five EMT-related genes signature predicts overall survival and immune environment in microsatellite instability-high gastric cancer.", "doi": "10.1002/cam4.4975", "pmid": "35789544", "authors": ["Mili Zhang", "Can Cao", "Xu Li", "Qisheng Gu", "Yixin Xu", "Ziyan Zhu", "Duogang Xu", "Shanshan Wei", "Haonan Chen", "Yuqin Yang", "Hugh Gao", "Liang Yu", "Jikun Li"], "journal": "Cancer medicine", "year": 2023, "abstract": "BACKGROUND: Microsatellite instability-high (MSI-H) subgroup of gastric cancer (GC) is characterized by a high tumor mutational burden, increased lymphocytic infiltration, and enhanced inflammatory cytokines. GC patients with MSI-H status have a good response to immune checkpoint blockade management. However, heterogeneity within the subtype and the underlying mechanisms of shaping tumor microenvironments remain poorly understood.\nMETHODS: RNA expression levels and clinical parameters of GC were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. The data were analyzed using single-sample Gene Set Enrichment Analysis (ssGSEA), univariate Cox regression, multivariate Cox regression, and Least Absolute Shrinkage Selection Operator (LASSO) regression. In addition, multiplex immunohistochemistry (mIHC) was used in our clinical cohort for the tumor microenvironment study.\nRESULTS: By ssGSEA and survival analysis, the EMT signaling pathway was identified as a representative pathway, which can stratify the patients with MSI-H GC with significant survival predictive power. Then, a novel representative EMT-related five-gene signature (namely CALU, PCOLCE2, PLOD2, SGCD, and THBS2) was established from EMT signaling gene set, which sensitivity and specificity were further validated in the independent GEO database (GSE62254) cohort for disease outcome prediction. Based on public single-cell data and in situ immunohistochemistry, we found that most of these five genes were abundantly expressed in cancer-associated fibroblasts. Furthermore, patients with high or low risk divided by this five-gene signature exhibited a strong correlation of the distinct patterns of tumor immune microenvironment. By mIHC staining of sections from 30 patients with MSI-H status, we showed that the patients with better prognoses had the increased infiltration of CD8+ cells in the primary tumoral tissue.\nCONCLUSION: Our study developed a simple five-gene signature for stratifying MSI-H GC patients with survival predictive power.", "claims": [{"id": "claim-method", "statement": "The data were analyzed using single‐sample Gene Set Enrichment Analysis (ssGSEA), univariate Cox regression, multivariate Cox regression, and Least Absolute Shrinkage Selection Operator (LASSO) regression.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35789544", "locator": "sections[0] \"Abstract\" paragraph 2", "quote": "The data were analyzed using single‐sample Gene Set Enrichment Analysis (ssGSEA), univariate Cox regression, multivariate Cox regression, and Least Absolute Shrinkage Selection Operator (LASSO) regression."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The original contributions proposed in the study are included in the article/supplementary Materials, which can be further queried from the corresponding authors.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35789544", "locator": "sections[28] \"DATA AVAILABILITY STATEMENT\" paragraph 2", "quote": "The original contributions proposed in the study are included in the article/supplementary Materials, which can be further queried from the corresponding authors."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The five-gene prognostic signature predicted overall survival in the TCGA MSI-H gastric cancer cohort with an AUC of 0.8333 and achieved an AUC of 67% in the GSE62254 validation cohort.", "kind": "quantitative", "target": {"value": 67.0, "unit": "per cent", "tolerance": null, "source": "In addition, we also assessed the predictive ability of this signature to significantly stratify MSI‐H patients, as determined by the ROC curve of the model with the AUC value of 67% (Figure 4C)."}, "evidence": [{"asset": "source:pmid:35789544", "locator": "sections[17] \"Identification of survival‐related genes in MSI‐H GC\" paragraph 2", "quote": "The areas under the curve (AUCs) for the risk score in predicting OS were 0.8333 (Figure 3E)."}, {"asset": "source:pmid:35789544", "locator": "sections[18] \"External validation of the five‐gene prognostic signature\" paragraph 2", "quote": "In addition, we also assessed the predictive ability of this signature to significantly stratify MSI‐H patients, as determined by the ROC curve of the model with the AUC value of 67% (Figure 4C)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The five-gene prognostic signature predicted overall survival in the TCGA MSI-H gastric cancer cohort with an AUC of 0.8333 and achieved an AUC of 67% in the GSE62254 validation cohort.", "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:35789544"], "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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In addition, multiplex immunohistochemistry (mIHC) was used in our clinical cohort for t", "Based on public single-cell data and in situ immunohistochemistry, we found that most of these five genes were", "in the tumor microenvironment, we performed immunofluorescence staining in our samples identified as MSI‐H", "TISCH (http://tisch.comp‐genomics.org/). 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