Integrated analysis of the underlying immunomodulator and survival signature of STON1 gene in kidney renal clear cell carcinoma

Abstract

Background Stonin 1 (STON1) is an endocytic protein but its role in cancer remains unclear. Here, we investigated the role of STON1 in kidney renal clear cell carcinoma (KIRC). Methods We undertook bioinformatics analyses of a series of public databases to determine the expression and clinical significance of STON1 in KIRC and focused on STON1-related immunomodulator and survival signatures. A nomogram model integrating clinicopathological characteristics and risk scores for KIRC was established and validated. Results Through TGCA and GEO databases, STON1 mRNA was found to be significantly downregulated in KIRC compared with normal controls, and decreased STON1 was related to grade, TNM stage, distant metastasis, and vital status of KIRC. Furthermore, OncoLnc, UALCAN, Kaplan–Meier, and GEPIA2 analyses supported that KIRC patients with high STON1 expression had better overall survival. STON1 was positively associated with mismatch proteins including MLH1, PMS2, MSH2, MSH6 and EpCAM, and was negatively correlated with tumor mutational burden. Interestingly, arm-level deletion of STON1 was clearly related to the abundance of immune cells and the infiltration abundance in the majority of 26 immune cell types that were positively related to STON1 mRNA level in the TIMER database. The TISIDB database revealed 21 immunostimulators and 10 immunoinhibitors that were obviously related to STON1 in KIRC. In univariate and multivariate Cox regression analyses, CTLA4 , KDR , LAG3 , PDCD1 , HHLA2 , TNFRSF25 , and TNFSF14 were screened to establish a risk score model, and the low-risk group had a better prognosis for KIRC. Furthermore, a nomogram integrating clinicopathological characteristics and risk score had better accuracy and practicability in predicating the survival of KIRC patients. Conclusions Decreased STON1 expression in KIRC leads to clinical progression and poor survival. Mechanically, loss of STON1 is associated with the aberrant immune microenvironment in KIRC. Integrated clinicopathological characteristics and risk score derived from STON1 -related immunomodulators can aid the prediction of KIRC survival.