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.
MicroRNAs (miRNAs) play an important role in the occurrence of non-obstructive azoospermia (NOA). Nevertheless, there is still a lack of research on the molecular mechanisms by which miRNAs regulate target genes to mediate NOA at present. In this study, we obtained NOA-related miRNA datasets from the GEO database and applied differential expression matrices combined with weighted correlation network analysis (WGCNA) and LASSO regression to identify four key miRNAs. Based on the miRDB database, the target genes of these miRNAs were predicted and intersected with the differentially expressed genes (DEGs) in the NOA transcriptome datasets. This intersection resulted in the identification of 18 DEGs. The spermatogenesis score model revealed a significant positive correlation between the overall expression level of these 18 DEGs and spermatogenesis scores, suggesting their potential involvement in NOA development. These 18 DEGs were subsequently incorporated into machine learning, leading to the identification of four hub genes with high diagnostic value: MGARP, FER1L5, SNX2, and PAPOLB. In the NOA mouse model, MGARP and SNX2 were upregulated, whereas FER1L5 and PAPOLB were downregulated, consistent with the expression trends observed in the NOA datasets. These findings indicate that MGARP, FER1L5, SNX2, and PAPOLB may serve as novel biomarkers for NOA, providing a theoretical and experimental foundations for elucidating its mechanisms and improving clinical diagnosis.

