Cardiac-Specific Gene TNNI3 Acts as a Potential Oncogene for Papillary Renal Cell Carcinoma

Abstract Background: The TNNI3 gene, responsible for encoding the inhibitory subunit of the troponin complex known as cardiac troponin I (cTnI), has significant implications in cardiology research. Despite reports of its abnormal expression in human carcinoma cells, the precise functions of TNNI3 in cancer remain largely unexplored. The present study seeks to examine the prognostic significance of TNNI3 in papillary renal cell carcinoma (pRCC). Methods: The mRNA expression profiles were acquired from the Cancer Genome Atlas (TCGA) database to identify candidate prognostic genes using univariate Cox analysis, log-rank test, and the least absolute shrinkage and selection operator (LASSO) analysis. A prognostic risk formula was established through multivariable Cox regression analysis. Additionally, Gene Ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, and immune-related function analyses were conducted. Furthermore, western blot, cell proliferation assay, and wound healing assay were employed to validate the in vitro biological effects of TNNI3. Results: A total of 361 differentially expressed genes (DEgenes) were found to be correlated with TNNI3 expression. A prognostic risk formula including the genes PTPRH, LGR5, and DMRT3 was then formulated. Notably, the low-risk group demonstrated superior overall survival (OS) outcomes compared to the high-risk group, as observed in both the training and validation cohorts. To further elucidate the potential functions of these three genes, a target gene network was constructed. Subsequent GO and KEGG analyses revealed their involvement in the Wnt signaling pathway, which was confirmed through western blot experiment. Furthermore, cellular experiments demonstrated that TNNI3 promotes the proliferation and metastasis of pRCC cells. Lastly, immune analyses indicated that increased expression of TNNI3 in pRCC is associated with a poorer response to immunotherapy. Conclusion: TNNI3 might function as an oncogene via activating Wnt signaling pathway in pRCC and a three-gene signature related to TNNI3 could serve as a prognostic biomarker for pRCC.