Intratumor stromal proportion predicts aggressive phenotype of gastric signet ring cell carcinomas

The aim of this study was to evaluate the prognostic significance of the intratumor stromal proportion in gastric signet ring cell (SRC) carcinomas. Cancer stroma, as exemplified by cancer-associated fibroblasts (CAFs), plays critical roles in cancer proliferation, invasion, and metastasis. One hundred seventy-five SRC carcinoma cases were classified according to the intratumor desmoplastic stromal proportion to then analyze the clinicopathologic characteristics of stroma-rich cases. We also investigated the impact of CAFs on the migration as well as on the phenotypic changes of gastric SRC carcinomas in vitro. Furthermore, we performed RNA sequencing of a pair of CAFs and normal-tissue-associated fibroblasts. Stroma-rich SRC carcinomas (64 of 175 cases, 36.5%) were associated with female patients (P = 0.045), large tumor size (P = 0.007), higher T category (P