Calbindin S100A16 Promotes Renal Cell Carcinoma Progression and Angiogenesis via the VEGF/VEGFR2 Signaling Pathway

Abstract

Purpose. Recent research has indicated that the calcium-binding protein S100A16 promotes carcinogenesis and tumor growth in several forms of cancer. The objective of this study was to examine the relationship between S100A16 and renal cell cancer. Methods. By using The Cancer Genome Atlas (TCGA) database, the differentially expressed gene S100A16 was identified, and its appearance and link to the prognosis of persons with renal cancer were confirmed. Cox regression was used in multivariate analysis, and a nomogram was developed for internal validation. The correlation between S100A16 and immune cells was analyzed in the TIMER database. Moreover, the potential mechanism of action was investigated utilizing GO and KEGG enrichment analyses. Proliferation, migration, and angiogenesis were investigated in vitro, and the involvement of S100A16 in the undesirable biological events of renal cell carcinoma (RCC) was further explored. Results. S100A16 was the differentially expressed molecule identified through database screening. Malignant tissues showed higher S100A16 expression than noncancerous tissues, and S100A16 expression was mostly localized in the cytoplasm. According to the TCGA and KM-plotter datasets, patients with RCC and low S100A16 expression had superior OS, PFI, and DSS. The C-index of the nomogram was 0.754 (0.726–0.782), and the accuracy of the prediction model was high. The TIMER database shows that the expression of S100A16 is associated with immune infiltration and may play an important role in promoting tumor cell immune escape in the RCC tumor microenvironment. S100A16 may influence the biological processes of RCC via the VEGF/VEGFR2 signaling route and PI3K-Akt signaling pathway and through P53 alteration and cell cycle according to the gene enrichment technique. In vitro cytological experiments demonstrated that S100A16 knockdown can inhibit the proliferation and migration of renal cancer cells and the expression levels of VEGF, VEGFR2, and phosphorylated AKT within renal cancer cells, thereby inhibiting angiogenesis in renal cancer cells and resulting in a poor prognosis of RCC. Conclusion. A decrease in S100A16 expression may dramatically increase the OS, PFI, and DSS of patients with RCC and may thus be used as a biomarker for predicting RCC. It may be associated with the immune infiltration of RCC and play a crucial role in the immune evasion of tumor cells within the RCC microenvironment. Intervention of s100a16 can promote the progression and angiogenesis of renal cell carcinoma through the VEGF/VEGFR2 signal transduction pathway and lead to poor prognosis of renal cell carcinoma. These findings suggest a potential target for the development of anticancer strategies for renal cancer.