SLC9A1 Binding mTOR Signaling Pathway-Derived Risk Score Predicting Survival and Immune in Clear Cell Renal Cell Carcinoma

Abstract

Objective. Clear cell renal cell carcinoma (ccRCC) is one of the common renal cell carcinomas (RCC) with a high risk of recurrence. Considering that SLC9A1 is involved in various cellular physiological processes and probably mediates the course of mTOR signaling in tumors, this study constructed a risk model for SLC9A1 combined with mTOR signaling in ccRCC, aiming at better predicting the prognosis of patients. Methods. ccRCC expression matrices were downloaded from TCGA and ICGC databases to compare the expression of SLC9A1 in TCGA, and qRT-PCR was adopted to validate the SLC9A1 expression in different RCC cells and normal kidney cells. The CIBERSORT and ESTIMATE algorithms were used to assess samples for immunity. mTOR signaling-associated genes were downloaded from the KEGG website, and then the genes were adopted to screen genes associated with SLC9A1 expression and mTOR signaling pathway colleagues, based on which univariate COX regression and lasso regression Cox analyses were conducted to construct a ccRCC prognostic risk model. ROC curves and nomograms were used to assess the validity of the models. Results. ccRCC tumor samples showed lower SLC9A1 expression than normal samples, as also evidenced by qRT-PCR. The SLC9A1 expression was highly correlated with tumor immunity. Totally, 564 key genes associated with both SLC9A1 expression and mTOR signaling were screened out, and the risk model consisting of 11 gene signatures was constructed in ccRCC based on the 564 genes. Since patients at a high risk had poorer survival outcomes, the high-risk group presented poorer immunotherapy outcomes. Moreover, a higher clinical grade of patients suggested a higher risk score. The risk score can serve as one independent prognostic factor for the prognosis prediction of ccRCC patients. Conclusion. An extremely promising prognostic indicator for ccRCC based on SLCA9A1 and mTOR signaling has been constructed to provide reference for clinical treatment.