循环miRNA作为晚期胆管癌化学免疫治疗潜在的预测生物标志物：II期T1219研究的事后分析

Circulating miRNAs as potentially predictive biomarkers for chemoimmunotherapy in advanced biliary tract cancer: a post-hoc analysis of the phase II T1219 study.

作者信息

Chiang Nai-Jung, Tang Cheng-Yu, Bai Li-Yuan, Chang Po-Chang, Chen Wei-Ming, Kang Shih-Ting, Chen San-Chi, Chen Ming-Huang, Hsieh Jason Chia-Hsun

机构信息

Department of Oncology, Taipei Veterans General Hospital, Taipei, Taiwan.

School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.

出版信息

NPJ Precis Oncol. 2025 Aug 30;9(1):307. doi: 10.1038/s41698-025-01099-x.

DOI:10.1038/s41698-025-01099-x

PMID:40885799

Abstract

Circulating microRNAs (miRNAs) have not been investigated as predictive biomarkers in patients with advanced biliary tract cancer (ABTC) who received chemoimmunotherapy. In the single-arm phase II T1219 trial, 46 patients with ABTC received first-line nivolumab, gemcitabine, and S-1 treatment. Plasma samples were prospectively collected at baseline and 6 weeks after treatment for miRNA profiling. Among the 167 miRNAs analyzed, the baseline levels of hsa-miR-16-5p, hsa-miR-93-5p, and hsa-miR-126-3p were significantly elevated in the responders. High hsa-miR-16-5p expression was correlated with longer progression-free survival (hazard ratio [HR] = 0.44, 95% confidence interval [CI] = 0.12-0.85, p = 0.025) and overall survival (HR = 0.34, 95% CI = 0.07-0.7, p = 0.01). Post-treatment miRNA changes (e.g., hsa-miR-129-5p and hsa-miR-1254) were observed but were not significantly associated with survival. This study identified a three-miRNA signature with potential predictive value for chemoimmunotherapy in ABTC. Trial registration: NCT04172402, date of registration 2019/11/18.

摘要

循环微小RNA（miRNA）尚未作为接受化学免疫疗法的晚期胆管癌（ABTC）患者的预测生物标志物进行研究。在单臂II期T1219试验中，46例ABTC患者接受了一线纳武单抗、吉西他滨和S-1治疗。在基线和治疗后6周前瞻性收集血浆样本用于miRNA分析。在分析的167种miRNA中，应答者中hsa-miR-16-5p、hsa-miR-93-5p和hsa-miR-126-3p的基线水平显著升高。高hsa-miR-16-5p表达与更长的无进展生存期（风险比[HR]=0.44，95%置信区间[CI]=0.12-0.85，p=0.025）和总生存期（HR=0.34，95%CI=0.07-0.7，p=0.01）相关。观察到治疗后miRNA的变化（如hsa-miR-129-5p和hsa-miR-1254），但与生存期无显著关联。本研究确定了一种三miRNA特征，对ABTC化学免疫疗法具有潜在预测价值。试验注册：NCT04172402，注册日期2019/11/18。