Decorin as a key marker of desmoplastic cancer-associated fibroblasts mediating first-line immune checkpoint blockade resistance in metastatic gastric cancer

Background: Gastric cancer (GC) remains a significant cause of cancer-related mortality worldwide. Despite the transformative impact of immune checkpoint blockade (ICB) therapies across various cancers, only a minority of patients with metastatic GC (mGC) benefit, emphasizing the urgent need for precise biomarkers to predict therapeutic responses and optimize patient selection.Methods: In this multi-omics study, we conducted whole exome and transcriptome sequencing on 12 tumors from mGC patients treated with nivolumab as first-line therapy. To validate our findings, we performed additional whole transcriptome sequencing on 17 internal and 45 public datasets from patients who received ICB therapy as second or third-line treatment. Comprehensive multi-omics analyses were conducted using single-cell RNA sequencing, spatial transcriptome sequencing, and public databases.