FXYD3 Expression Predicts Poor Prognosis in Renal Cell Carcinoma with Immunosuppressive Tumor Microenvironment.

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However, the prognostic value of FXYD3 expression in clear renal cell carcinoma (KIRC) is unclear. Therefore, we evaluated the clinical data with tumor-infiltrating lymphocytes (TILs) and immunoinhibitory gene expression data using The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) dataset (GSE29609). First, the FXYD3 high KIRC patients had distinct clinical characteristics, including age, sex, disease stage, histological grade, and hypoxia-related gene expressions. Next, FXYD3 gene expression was correlated with poor overall survival in both TCGA and GSE29609 cohorts. The ESTIMATE algorithm revealed that higher FXYD3 mRNA levels were associated with increased infiltration of immune cells and tumor purity. Moreover, the FXYD3 high KIRC tissue harbored increased TILs such as B cells, CD8+ T cells, and M1 macrophage, whereas NK cells and neutrophils were decreased. In addition, we showed FXYD3 was co-expressed with several immunoinhibitory genes related to T cell exhaustion such as LGALS9, CTLA4, BTLA, PDCD1, and LAG3. In conclusion, FXYD3 is an unfavorable prognostic biomarker associated with hypoxia, pro-tumor TILs, and T cell exhaustion.", "claims": [{"id": "claim-method", "statement": "Kaplan-Meier curves were plotted for overall survival (OS).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35892856", "locator": "sections[3] \"2.1. Survival Analysis with FXYD3 mRNA Levels in the Public Database\" paragraph 2", "quote": "Kaplan-Meier curves were plotted for overall survival (OS)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The authors downloaded the TCGA gene expression data (https://www.cbioportal.org/) and GSE29609 (https://www.ncbi.nlm.nih.gov/geo/).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35892856", "locator": "sections[18] \"notes\" paragraph 1", "quote": "The authors downloaded the TCGA gene expression data (https://www.cbioportal.org/) and GSE29609 (https://www.ncbi.nlm.nih.gov/geo/)."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Patients with higher FXYD3 gene expressions had shorter OS on TCGA dataset (Hazard ratio (HR) (95% confidence interval (CI)): 1.64 (1.09–2.47), p = 0.019, Figure 1A).", "kind": "quantitative", "target": {"value": 95.0, "unit": "per cent", "tolerance": null, "source": "Patients with higher FXYD3 gene expressions had shorter OS on TCGA dataset (Hazard ratio (HR) (95% confidence interval (CI)): 1.64 (1.09–2.47), p = 0.019, Figure 1A)."}, "evidence": [{"asset": "source:pmid:35892856", "locator": "sections[9] \"3.2. Prognostic Impact of FXYD3 Gene Expression in KIRC\" paragraph 2", "quote": "Patients with higher FXYD3 gene expressions had shorter OS on TCGA dataset (Hazard ratio (HR) (95% confidence interval (CI)): 1.64 (1.09–2.47), p = 0.019, Figure 1A)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Patients with higher FXYD3 gene expressions had shorter OS on TCGA dataset (Hazard ratio (HR) (95% confidence interval (CI)): 1.64 (1.09–2.47), p = 0.019, Figure 1A).", "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:35892856"], "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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