Department of Digestive Surgery.
Department of Endoscopic Surgery, Air Force 986th Hospital, Fourth Military Medical University, Xian.
Int J Surg. 2023 May 1;109(5):1094-1104. doi: 10.1097/JS9.0000000000000249.
The timing of surgery for patients with gastric cancer (GC) who undergo neoadjuvant chemotherapy (neoCT) was mainly guided by serial radiologic imaging. However, an earlier assessment was indispensable to avoid delayed treatment for nonresponders and excessive toxicity for responders. Our previous study has identified circulating extracellular vesicles-derived lncRNA-GC1 as a biomarker for early detection and monitoring progression of GC. However, the potential role of neoCT remains poorly understood.
In this explorative biomarker analysis, we conducted a multi-cohort study to examine longitudinal levels of circulating extracellular vesicles-derived lncRNA-GC1 in 798 patients enrolled in the RESONANCE study (NCT01583361). Both circulating extracellular vesicles-derived lncRNA-GC1 and traditional gastrointestinal biomarkers were assessed at defined time nodes. Computed tomography (CT) scans were performed before treatment and 8-10 weeks and assessed based on the RECIST criteria.
Circulating extracellular vesicles-derived lncRNA-GC1 could be detected in 96.3% of patients at baseline, and significant reductions were observed before cycle 2 (P<0.0001). Levels of circulating extracellular vesicles-derived lncRNA-GC1 showed a stronger correlation with tumor burden and exhibited earlier dynamic changes than the traditional gastrointestinal biomarkers during the first cycle of neoCT. Strong agreement was observed between circulating extracellular vesicles-derived lncRNA-GC1 response (reduction >50%) and radiographic response (Cohen's κ, 0.704). Importantly, circulating extracellular vesicles-derived lncRNA-GC1 maintained predictive value in two external cohorts. Patients with circulating extracellular vesicles-derived lncRNA-GC1 response showed superior disease-free survival [hazard ratio (HR), 0.6238; 95% CI, 0.4095-0.9501; P=0.0118] and overall survival (HR, 0.6131; 95% CI, 0.4016-0.9358; P=0.0090).
Circulating extracellular vesicles-derived lncRNA-GC1 is an early marker of neoCT efficacy and predicts superior survival in GC patients treated with neoCT.
接受新辅助化疗（neoCT）的胃癌（GC）患者的手术时机主要由连续影像学检查指导。然而，为了避免对无应答者治疗延迟和对应答者毒性过大，早期评估是必不可少的。我们之前的研究已经确定了循环细胞外囊泡衍生的 lncRNA-GC1 作为早期检测和监测 GC 进展的生物标志物。然而，neoCT 的潜在作用仍知之甚少。
在这项探索性生物标志物分析中，我们对 RESONANCE 研究（NCT01583361）中招募的 798 名患者进行了多队列研究，以检测循环细胞外囊泡衍生的 lncRNA-GC1 的纵向水平。在定义的时间节点评估循环细胞外囊泡衍生的 lncRNA-GC1 和传统的胃肠生物标志物。在治疗前和 8-10 周进行计算机断层扫描（CT）扫描，并根据 RECIST 标准进行评估。
在基线时，96.3%的患者可检测到循环细胞外囊泡衍生的 lncRNA-GC1，并且在第 2 周期前观察到显著降低（P<0.0001）。在 neoCT 的第一个周期中，循环细胞外囊泡衍生的 lncRNA-GC1 与肿瘤负担的相关性更强，并且表现出比传统胃肠生物标志物更早的动态变化。循环细胞外囊泡衍生的 lncRNA-GC1 反应（降低>50%）和影像学反应之间观察到强烈的一致性（Cohen's κ，0.704）。重要的是，循环细胞外囊泡衍生的 lncRNA-GC1 在两个外部队列中保持预测价值。具有循环细胞外囊泡衍生的 lncRNA-GC1 反应的患者无疾病生存时间更长[风险比（HR），0.6238；95%置信区间，0.4095-0.9501；P=0.0118]和总生存时间（HR，0.6131；95%置信区间，0.4016-0.9358；P=0.0090）。
循环细胞外囊泡衍生的 lncRNA-GC1 是 neoCT 疗效的早期标志物，可预测接受 neoCT 治疗的 GC 患者的生存优势。
