Here, we performed an integrative multi-omics analysis across seven digestive cancer types and identified a conserved four-gene signature-<i>DCN</i>, <i>COL10A1</i>, <i>CTHRC1</i>, and <i>TREM2</i>-that is consistently enriched in matrix cancer-associated fibroblasts (mCAFs) and myeloid cells. Here, TREM2 is linked to cancer.