Potential of SERINC2 as a biomarker in tumor prognosis and immunology: analysis from pan-cancer studies.

Abstract

Serine incorporator (SERINC) is a family of transmembrane protein involved in lipid synthesis. Among its family members, SERINC2 has been implicated in tumor pathogenesis. Pancreatic carcinoma (PAAD), a highly malignant tumor characterized by an extremely poor prognosis, lacks effective biomarkers. To date, the association between SERINC2 and pan-cancer or tumor immunity remains unreported in the literature. Consequently, investigating the utility of SERINC2 for prognostic prediction in PAAD lays the groundwork for developing diagnostic biomarkers and SERINC2-targeted immunotherapy strategies. In this study, we used the transcriptional data in normal and tumor tissues from The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx) and Human Protein Atlas (HPA). Analysis of publicly available data (TCGA, GTEx, HPA) revealed significant SERINC2 overexpression in multiple cancers, which was associated with advanced clinicopathological stage (P<0.05). Analysis of the Genomic Stability Associated Cancer Analysis (GSCA) database revealed a significant positive correlation between copy number variation (CNV) and SERINC2 expression levels. Conversely, DNA methylation was inversely correlated with SERINC2 expression (P<0.05). Further investigation utilizing TCGA database demonstrated that SERINC2 expression was significantly associated with the expression of immune checkpoint molecules, response to immunotherapy, and the extent of immune cell infiltration. Notably, a negative correlation was observed between SERINC2 expression and the tumor microenvironment (TME) score in most cancer types analyzed (P<0.05). We constructed a prognostic model for PAAD based on 25 differentially expressed genes (DEGs) identified from the TCGA cohort using the "limma" package. This model effectively stratified patients into high- and low-risk groups with significantly distinct survival outcomes. Immunohistochemical (IHC) analysis of 54 PAAD patient samples validated that high SERINC2 expression was significantly associated with poorer prognosis; patients with high expression had a significantly shorter median overall survival (19.67 vs 50.52 months, P=0.029). Collectively, our findings provide a rationale for developing SERINC2-based diagnostic biomarkers and immunotherapeutic strategies.