Integrative analysis of SEC13: a prognostic predictor and immunotherapeutic target.

[BACKGROUND] The SEC13 is a multifaceted gene implicated in mTORC1 signaling regulation and the maintenance of genomic stability. Its function in cancer is complex, displaying potential oncogenic as well as potential tumor-suppressive roles across different malignancies. Therefore, this study aimed to investigate SEC13 expression, prognostic value, and its relationship with immune checkpoints across different cancer types.

[METHODS] Differential expression analysis, diagnostic analysis, and prognostic analysis were analyzed with The Cancer Genome Atlas and Human Protein Atlas database. The potential related genes were analyzed by utilizing Gene Expression Omnibus and clinical breast cancer samples. GO (Gene Ontology) and GSEA (Gene Set Enrichment Analysis) were used to elucidate the potential role of SEC13. TMB (tumor mutation burden), MSI (microsatellite instability), immune checkpoint, and immune cell infiltration were also analyzed to indicate its potential role in immune feature. To validate the functional impact of SEC13, its effects on cell proliferation and cell cycle distribution were assessed using CCK-8 assays and flow cytometry in MDA-MB-231 and MCF7 breast cancer cells following SEC13 knockdown.

[RESULTS] SEC13 was highly expressed in 14 tumor types and lowly expressed in 2 tumor types. High expression of SEC13 was associated with worse overall survival, disease-specific survival, and progression-free interval in breast cancer, liver hepatocellular carcinoma, and sarcoma. SEC13 expression was correlated with several co-expressed genes (e.g., MED8, RPN1) and was enriched in cell cycle pathway. Functionally, SEC13 knockdown was found to reduce the S-phase cell proportion and inhibit cell proliferation. In addition, SEC13 exhibited relationships with TMB and MSI, immune checkpoint, and immune cell infiltration.

[CONCLUSION] This study underscores the significant expression differences and prognostic implications of SEC13 in various cancers, emphasizing its potential as a biomarker and therapeutic target.