Pan-cancer analysis of the oncogenic effect of SorCS1 in human tumors and its correlation with LRP2 protein

Abstract

Abstract Background: SorCS1 is a member of the mammalian type –Ⅰtransmembrane receptor family containing Vps10p structural domain. According to known results, SorCS1 plays important role in ligands absorption and trafficking, and is related to many nervous diseases. LRP2 is low density lipoprotein-related protein 2 (LRP2) or megalin, is a multi-ligand endocytic receptor. Up to date, more and more emerging cellular or animal-based evidence supports a relationship between SorCS1 and cancer; in the meanwhile, SorCS1 shows some correlation with LRP2, bust there is no relevant analysis data showing how SorCS1 works with other factors and LRP2. Therefore, we explored the potential oncogenic role of SorCS1，and correlation with LRP2 in a variety of cancers using the TCGA (The Cancer Genome Atlas) and GEO (Gene Expression Omnibus) databases. Methods: The related data of human tumor patients were obtained from the TCGA and GEO databases, respectively. The TIMER and GEPIA2 database was used to analyze the expression of SorCS1 and LRP2 in tumors and their survival analysis. The UALCAN database was used to analyze the differences in the expression of SorCS1 and LRP2 in tumor staging. Then, the TIMER database was used for immune cell infiltration analysis, and the GEPIA2 database was used for the detection of genes associated with the SorCS1 gene and for enrichment analysis. Results: According to current studies, SorCS1 expression is usually lowly in most cancers but indeed is significantly correlated with the prognosis in several ones. In latter, our analyses showed a significant correlation between SorCS1 and LRP2, such as SKAM (Stomach adenocarcinoma), TGCT (Testicular Germ Cell Tumors), THCA (Thyroid carcinoma), UVM (Uveal Melanoma), and some other cancers. In the meanwhile, there was an increased extent of mutation in SorCS1. Our correlation analyses provide some understanding of the oncogenic role of SorCS1 and LRP2 in different tumors and their relevance. In addition, we detected correlations between SorCS1 and CD8+ immune cells or fibroblast infiltration in databases such as STAD. We counted potentially relevant genes for SorCS1 in various cancers and did KEGG and GO enrichment analyses of these genes, providing new ideas for the response pathways involved in SorCS1 in cancers. Conclusion: SorCS1 was aberrantly expressed in most tumors and shared the same expression trend as LRP2.