ABSTRACT 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.
Chen et al. (2025) studied this question.