Systematic analysis of RNASET2 gene as a potential prognostic and immunological biomarker in clear cell renal cell carcinoma

AbstractBackground RNASET2 has been identified as an oncogene with anti-angiogenic and immunomodulatory effects in a variety of cancers, but its function in clear cell renal cell carcinoma (ccRCC) remains unknown. Methods The RNASET2 expression matrix was extracted from the The Tumor Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets and analysed for diagnostic and prognostic value. RNASET2 mRNA expression was detected by quantitative polymerase chain reaction (qPCR) in ccRCC patients and renal cancer cell lines. Wound healing assay, transwell assay, western blotting, and tube formation assays were used to evaluate the function of RNASET2 in renal cancerin vitro. In addition, transcriptome sequencing was performed on knockdown RNASET2 kidney cancer cells to analyze their potential signaling pathways. Finally, the immune microenvironment and mutational status were evaluated to predict the potential mechanisms of RNASET2 involvement in renal cancer progression. Sensitivity to common chemotherapeutic and targeted agents was assessed according to the Genomics of Drug Sensitivity in Cancer (GDSC) database. Results RNASET2 expression was significantly upregulated in ccRCC tissues and renal cancer cell lines, predicting poor prognosis for patients.In vitroexperiments showed that silencing RNASET2 inhibited the migration and pro-angiogenic ability of renal cancer cells. Transcriptome sequencing suggested its possible involvement in the remodelling of the immune microenvironment in renal cell carcinoma. Finally, the results of public databases demonstrated that RNASET2-associated immune cell infiltration and gene mutations may lead to a poor prognosis of ccRCC and have some predictive power for drug sensitivity. Conclusions These finding suggests that RNASET2 is a promising biomarker for the diagnosis, prognosis and immunology of ccRCC and that it may be a novel target for immunotherapy of ccRCC.