Olfactory Receptor Expression Profiles in Clear Cell Renal Cell Carcinoma Reveal Potential Diagnostic and Prognostic Markers

BackgroundOlfactory receptors (ORs) are G protein-coupled receptors that are aberrantly expressed in various cancers, including clear cell renal cell carcinoma (KIRC). However, the roles of ORs in KIRC are unknown. This study aimed to comprehensively analyze the expression profiles of OR genes in KIRC and evaluate their potential as diagnostic and prognostic biomarkers. MethodsWe analyzed RNA-seq data from The Cancer Genome Atlas KIRC dataset, which contains 72 normal and 530 tumor samples. We selected OR genes with median transcripts per million (TPM) values of 1 or higher in at least one group (normal or tumor). Differential expression analysis was performed using the Students t-test or Wilcoxon rank-sum test. The diagnostic potential of OR genes was evaluated using receiver operating characteristic (ROC) curve analysis. Kaplan-Meier analysis was employed to assess the association between OR gene expression and patient survival. Sex-based differences in OR gene expression were also examined. ResultsWe identified 11 OR genes with significant changes in KIRC expression. Among them, OR2A4, OR51E1, and OR7E14P showed high diagnostic performance, with AUC values of 0.951, 0.924, and 0.910, respectively. Combining these three genes improved the AUC to 0.972. High OR2A20P expression was significantly associated with poorer prognosis, whereas high OR7E7P expression was associated with better prognosis. We also found sex-based differences in the expression of OR2A7, OR2I1P, and OR7E14P, with females exhibiting significantly higher expression. ConclusionsOur findings suggest that ORs, especially OR2A4, OR51E1, and OR7E14P, could serve as potential diagnostic markers for KIRC. OR2A20P and OR7E7P may represent promising prognostic markers. The observed sex-based differences in OR gene expression highlight the need for personalized treatment of KIRC. Further studies are warranted to validate these findings and elucidate the functional roles of ORs in the pathogenesis of KIRC.