Systematic Pan-Cancer Analysis of the Oncogenic and Immunological Function of Stanniocalcin-1 (STC1)

Abstract

Abstract Stanniocalcin 1 (STC1) plays an integral role in various cancers, but current studies provide limited information in pan-cancer. Here, we focus on its roles in prognosis and immunology in human cancers. Pan-cancer bulk sequencing data and online web tools were applied to analyze STC1’s correlations with prognosis,immune checkpoints (ICP), tumor mutational burden (TMB), microsatellite instability (MSI), cancer stemness, neoantigens and immune infiltratio in pan-cancer. We also used UALCAN, HPA, cBioPortal, Single-cell and GTAB database to explore the function of STC1 in different cancers. Moreover, multiple fluorescence staining was used to validate the association between STC1 expression and CD4+ and CD8+ T cells. Further, Western Blot was adopted to detect the expression of STC1 in Stomach adenocarcinoma (STAD) cells and tumor. We noticed that STC1 was highly expressed in most cancers and had strong relationships with prognosis, ICP, TMB, MSI, cancer stemness, and neoantigens. The utmost alteration frequency of STC1 was in patients with prostate adenocarcinoma and all of which were “Deep Deletion” kind. Single-cell and gene enrichment analysis indicated that abnormally expressed STC1 was significantly associated with epithelial-mesenchymal transition (EMT). Furthermore, we confirmed the up-regulated of STC1 in STAD cells and tumor tissue. In particular, the multiple fluorescence staining on STAD tissue chip confirmed that STC1 correlated with CD4+ and CD8+ T cells. This study identified that SCT1 was a novel oncogene, and it correlated with MSI, TMB, immune cells infiltration level and EMT. STC1 was highly associated with ICP and could be a novel target for tumor immunotherapy.