Plasma Small RNAs as Predictive and Monitoring Biomarkers for Combination Immunotherapy in Advanced Gastric Cancer

作者：Jian Fang, Yan Sun, Yuhui Yu, Zheng Fu, Yitong Tian, Yizhang Chen, Fen Guo, Jie Tang, Caiwang Yan, Xi Chen, Xi Chen, Xiaofeng Chen, Xiaofeng Chen, Guangfu Jin · 发表于：Cancer Medicine · 年份：2025 · DOI：10.1002/cam4.71339 · 被引用次数：3 · 研究领域：Cancer Immunotherapy and Biomarkers、MicroRNA in disease regulation、Ferroptosis and cancer prognosis

BACKGROUND: Immunotherapy has become a new standard treatment for advanced gastric cancer (aGC). However, current biomarkers are insufficient for accurately identifying true responders, emphasizing the need for novel biomarkers. METHODS: Between December, 2020, and October, 2023, we recruited 91 consecutive aGC patients (49 in the discovery and 42 in the validation cohorts). Plasma samples were collected at baseline and after two cycles of immunotherapy. We conducted small RNA (sRNA) next-generation sequencing on 140 samples. Additionally, we investigated previously reported potential biomarkers, including PD-L1 combined positive score (CPS), inflammation scores, and serological tumor biomarkers. RESULTS: In the discovery cohort, we identified two pre-treatment sRNAs significantly associated with response to immunotherapy: high levels of hsa-miR-3916 (p = 0.020) and low levels of hsa-miR-181d-5p (p = 0.046), confirmed in the validation cohort (p = 0.011 and p = 0.013, respectively). The AUCs for predicting response using these two sRNAs were 0.77 (95% CI; 0.62-0.93) and 0.83 (95% CI; 0.71-0.96), respectively. When integrating PD-L1 CPS with these two sRNAs, the AUCs were 0.82 (95% CI; 0.68-0.96) and 0.83 (95% CI; 0.70-0.97) for the discovery and validation cohorts, respectively. Furthermore, when combining PD-L1 CPS and serological tumor biomarkers with these two sRNAs, the AUCs were 0.89 (95% CI; 0.79-1.00) and 0.83 (95% CI; 0.70-0.96) for the discovery and validation cohort...