Multi‐Omics Analysis Reveals <i>OBSCN</i> as a Key Modulator of Tumor Microenvironment, Microbial Signatures and Clinical Outcomes in Gastric Cancer

Emerging evidence suggests that OBSCN, a giant cytoskeletal protein gene, plays multifaceted roles in cancer progression, yet its impact on gastric cancer (GC) remains poorly understood. Through integrative analysis of multi-omics datasets, we observe a close relationship between OBSCN expression and outcome of immunotherapy. Besides, elevated expression of OBSCN strongly associated with adverse disease free survival (DFS). Tumor-resident microbes, such as Fusobacterium, can impact the expression of microRNAs (miRNAs) targeting OBSCN. In terms of genomic alterations, mutational status of OBSCN is substantially associated with the alpha- and beta-diversity of intratumoral microbiome and patients with mutated OBSCN exhibit elevated higher tumor mutational burden (TMB) and better response to immunotherapy. Furthermore, machine learning models based on the OBSCN mutation-related gene signatures (OMRGS) achieve outstanding performance in prediction of response to immune checkpoint inhibitors. In summary, our findings position OBSCN as a novel molecular nexus linking genomic alterations, intratumoral microbiome dysbiosis, and immune infiltration in GC, providing a rationale for future biomarker-driven therapeutic strategies.