Pan-cancer analysis identifies NT5E as a novel prognostic biomarker on cancer-associated fibroblasts associated with unique tumor microenvironment

• DOI: 10.3389/fphar.2022.1064032
• Publication Date: 2022-12-07T05:00:57Z
• Authors: Xin-miao Xue; Yu-yang Liu; Xue-min Chen; Bing-yan Tao; Peng Liu; Han-wen Zhou; Chi Zhang; Li Wang; Yu-ke Jiang; Zhi-wei Ding; Wei-dong Shen; Jun Zhang; Shi-ming Yang; Fang-yuan Wang
• Keywords: Cancer-Associated Fibroblasts

Background: Ecto-5′-nucleotidase (NT5E) encodes the cluster of differentiation 73 (CD73), whose overexpression contributes to formation immunosuppressive tumor microenvironment and is related exacerbated prognosis, increased risk metastasis resistance immunotherapy various tumors. However, prognostic significance NT5E in pan-cancer obscure so far. Methods: We explored expression level cancers adjacent tissues revealed relationship between clinical outcomes by utilizing UCSC Xena database. Then, correlation analyses were performed evaluate immune infiltration via EPIC, MCP-counter CIBERSORT methods, enrichment analysis employed identify NT5E-interacting molecules functional pathways. Furthermore, we conducted single-cell explore potential role on based CancerSEA Meanwhile, gene set (GSEA) was also TISCH database signature explorer utilized epithelial-mesenchymal transition (EMT) each cell type. Results: The aberrant almost all cancer types, correlated with worse prognosis several cancers. Notably, overall survival (OS) pancreatic adenocarcinoma (PAAD), head neck squamous carcinoma (HNSC), mesothelioma (MESO), stomach (STAD), uveal melanoma (UVM) cervical endocervical (CESC) ( p < 0.01). NT5E-related that associated positively degree cancer-associated fibroblasts (CAFs) endothelial cells most Enrichment cellular component (CC) demonstrated critical part played cell-substrate junction, adherens focal adhesion external side plasma membrane. Finally, illuminated EMT function CAFs elevated basal (BCC), skin cutaneous (SKCM), HNSC PAAD. Conclusion: could serve as a biomarker for mechanism may be upregulated CAFs, which provides novel inspiration targeting high expression.