Clinical significance and potential molecular mechanisms of SYT15 expression in lung adenocarcinoma

Increasing evidence suggests that the synaptotagmin (SYT) family is associated with the development of multiple types of cancer, yet research on SYT15 remains limited. The aim of this study was to elucidate the clinical significance and possible molecular mechanisms of SYT15 expression in lung adenocarcinoma (LUAD). The expression, clinical value, cellular function and possible molecular mechanisms of SYT15 in LUAD were evaluated by using bioinformatics analysis combined with cellular experiments. In LUAD, SYT15 expression was downregulated. Notably, this reduced expression was negatively associated with patient survival but positively correlated with immune cell infiltration in the tumor microenvironment. Furthermore, SYT15 expression correlated with three key aspects: sensitivity to 20 distinct drugs, the expression of immune checkpoint genes (ICGs), and the efficacy of immunotherapy. SYT15 was most highly expressed in Mono/Macro, CD8Tex, and CD8T cells within LUAD tissues. Cellular experiments confirmed that SYT15 overexpression reduced the malignant phenotype of A549 and H1975 cells. RNA sequencing results showed that the PI3K/AKT signaling pathway was significantly enriched after overexpression of SYT15 in A549 cells, and qPCR and WB experiments confirmed significant downregulation of genes related to this pathway.. Further experiments confirmed that PI3K agonist 740Y-P reversed the regulatory effects of SYT15 overexpression on A549 cell malignant phenotype and the PI3K/Akt signaling pathway. In LUAD, SYT15 acts as a tumor suppressor by potentially regulating immune cell infiltration in the tumor microenvironment and inhibiting the expression of key PI3K/AKT pathway genes in A549 cells. Consequently, it holds promise as a novel prognostic marker and potential therapeutic target..