KDELC1 and TRMT1 Serve as Prognosis-Related SARS-CoV-2 Proteins Binding Human mRNAs and Promising Biomarkers in Clear Cell Renal Cell Carcinoma

KDELC1 和 TRMT1 作为与预后相关的 SARS-CoV-2 蛋白,可结合人类 mRNA,并有望成为透明细胞肾细胞癌的生物标志物。

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Abstract

BACKGROUND: SARS-CoV-2 proteins binding human mRNAs (SPBRs) have been proven to regulate a variety of tumor-related functions in different types of cancer. However, their biological roles and potential mechanisms in clear cell renal cell carcinoma (ccRCC) are still elusive. Herein, we investigate the expression and prognostic value of SPBRs in ccRCC through bioinformatics methods. METHODS: Data downloaded from the Cancer Genome Atlas (TCGA) database was used to screen differentially expressed SPBRs (DE-SPBRs) between ccRCC samples and noncancerous samples. Metascape was utilized to perform function and pathway enrichment analyses of these DE-SPBRs. Kaplan-Meier method of overall survival (OS) was used to assess the prognostic value of DE-SPBRs in ccRCC patients. Univariate and multivariate Cox regression analyses were applied to identify candidate SPBRs, which were independently associated with overall survival of ccRCC patients. Subsequently, several internationally renowned databases were employed to conduct a comprehensive analysis of candidate SPBRs to further investigate their roles and mechanisms in ccRCC. RESULTS: A total of 33 DE-SPBRs, including 18 upregulated SPBRs and 17 downregulated SPBRs, were screened between ccRCC samples and noncancerous samples. Among them, two candidate SPBRs, KDELC1 and TRMT1, were identified. Additionally, we observed that upregulated KDELC1/TRMT1 expression in ccRCC at both gene and protein levels was significantly associated with clinicopathological features. Furthermore, we found that KDELC1/TRMT1 genetic mutation has an unfavorable influence on prognosis of patients with ccRCC. Functional enrichment analysis revealed that KDELC1/TRMT1 was closely enriched in several vital biological processes and pathways. Finally, we noticed that KDELC1/TRMT1 was remarkably associated with immune infiltrates. CONCLUSION: In summary, we screened DE-SPBRs of ccRCC, which were enriched mainly in various biological and signaling pathways with tumor progression. Furthermore, we identified two candidate DE-SPBRs (KDELC1 and TRMT1), which could serve as promising biomarkers and therapeutic targets of patients with ccRCC.

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