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pmid:36845675
CXCL9 correlates with antitumor immunity and is predictive of a favorable prognosis in uterine corpus endometrial carcinoma.
Shen Xue · Xiao-Min Su · Li-Na Ke · Yu-Gang Huang
Frontiers in oncology · 2023 doi:10.3389/fonc.2023.1077780
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Complete file
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Here, we assessed the prognostic significance and potential mechanism of CXCL9 in UCEC.\nMethods: Firstly, bioinformatics analysis of the public cancer database, including the Cancer Genome Atlas / the Genotype-Tissue Expression project (TCGA+ GTEx, n=552) and Gene Expression Omnibus (GEO): GSE63678 (n=7), were utilized for the CXCL9 expression-related analysis in UCEC. Then, the survival analysis of TCGA-UCEC was performed. Futher, the gene set enrichment analysis (GSEA) was carried out to reveal the potential molecular signaling pathway in UCEC associated with CXCL9 expression. Moreover, the immunohistochemistry (IHC) assay of our validation cohort (n=124) from human specimens were used to demonstrate the latent significance of CXCL9 in UCEC.\nResults: The bioinformatics analysis suggested that CXCL9 expression was significantly upregulated in UCEC patients; and hyper-expression of CXCL9 was related to prolonged survival. the GSEA enrichment analysis showed various immune response-related pathways, including T/NK cell, lymphocyte activation, cytokine-cytokine receptor interaction network, and chemokine signaling pathway, mediated by CXCL9. In addition, the cytotoxic molecules (IFNG, SLAMF7, JCHAIN, NKG7, GBP5, LYZ, GZMA, GZMB, and TNF3F9) and the immunosuppressive genes (including PD-L1) were positively related to the expression of CXCL9. Further, the IHC assay indicated that the CXCL9 protein expression was mainly located in intertumoral and significantly upregulated in the UCEC patients; UCEC with high intertumoral CXCL9 cell abundance harbored an improved prognosis; a higher ratio of anti-tumor immune cells (CD4+, CD8+, and CD56+ cell) and PD-L1 was found in UCEC with CXCL9 high expression.\nConclusion: Overexpressed CXCL9 correlates with antitumor immunity and is predictive of a favorable prognosis in UCEC. It hinted that CXCL9 may serve as an independent prognostic biomarker or therapeutic target in UCEC patients, which augmented anti-tumor immune effects to furnish survival benefits.", "claims": [{"id": "claim-method", "statement": "We deployed both uni-and multiple Cox regression assays to characterize the effect of CXCL9 expression on survival time and other clinical features. For prognostic analysis, the log-rank test was applied.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36845675", "locator": "sections[10] \"Statistical analysis\" paragraph 2", "quote": "We deployed both uni-and multiple Cox regression assays to characterize the effect of CXCL9 expression on survival time and other clinical features. For prognostic analysis, the log-rank test was applied."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The original contributions presented in the study are included in the article/Supplementary Material. Further inquiries can be directed to the corresponding authors. 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All publicly available datasets involved in this work are from TCGA (https://portal.gdc.cancer.gov/) and GEO (https://www.ncbi.nlm.nih.gov/geo/)."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Overexpressed CXCL9 correlates with antitumor immunity and is predictive of a favorable prognosis in UCEC.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:36845675", "locator": "sections[0] \"Abstract\" paragraph 4", "quote": "Overexpressed CXCL9 correlates with antitumor immunity and is predictive of a favorable prognosis in UCEC."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Overexpressed CXCL9 correlates with antitumor immunity and is predictive of a favorable prognosis in UCEC.", "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:36845675"], "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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