Background: The TYMP gene encodes an important nucleoside metabolism enzyme which is a rate-limiting enzyme for chemotherapeutic drug metabolism. Previous studies have shown that TYMP is highly expressed in many different tumors, promoting invasiveness and progression, and that it helps to predict the response to chemotherapeutic drugs. However, the role of TYMP in tumor immunity and prognosis remains largely unclear. The purpose of this pan-cancer analysis was to acquire more data on the function of TYMP function and its clinical significance.
Methods: To access the TYMP expression, we accessed datasets from The Cancer Genome Atlas (TCGA), Oncomine, Gene Expression Profiling Interactive Analysis (GEPIA), Cancer Cell Line Encyclopedia (CCLE) databases, and analyzed its differential expression between paired tumor and normal samples. We employed PrognoScan and Kaplan-Meier plotter for survival analyses. TYMP mutations were analyzed using cBioPortal. Correlations of TYMP with tumor stage, tumor mutational burden (TMB), microsatellite instability (MSI), immune checkpoint genes (ICGs), and immune cell infiltration were estimated via bioinformatics tools and methods. The CellMiner database was used to predict drug response. Gene set enrichment analysis (GSEA) was applied to explore the biological functions of TYMP in different tumors.
Results: Our results indicated that TYMP was overexpressed and also significantly associated with a worse prognosis in several human cancers, such as kidney clear cell carcinoma (KIRC) and lower grade glioma (LGG). TYMP was also associated with TMB, MSI, and ICGs across a variety of malignancies. TYMP was most significantly correlated with immune cell infiltration in five tumors, namely, breast cancer (BRCA), cervical cancer (CESC), KIRC, skin cutaneous melanoma (SKCM), and stomach adenocarcinoma (STAD). Moreover, TYMP expression predicted sensitivity to chemotherapy drugs and also influenced relevant biological pathways, according to enrichment analysis.
Conclusions: According to the results of this comprehensive analysis, TYMP is associated with prognosis and tumor immunology, which might make it be a potential therapeutic target for cancer treatment.
Keywords: TYMP; immune infiltration; pan-cancer analysis; prognosis; tumor mutational burden (TMB).
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