Matsutoka Koichi, Shoda Katsutoshi, Higuchi Yudai, Nakayama Takashi, Saito Ryo, Maruyama Suguru, Takiguchi Koichi, Nakata Yuki, Furuya Shinji, Shiraishi Kensuke, Kawaguchi Yoshihiko, Amemiya Hidetake, Masuda Kiyoshi, Ichikawa Daisuke
First Department of Surgery, Faculty of Medicine, University of Yamanashi, Chuo, Yamanashi, Japan.
Kawasaki Medical School, Okayama, Japan.
Ann Surg Oncol. 2025 Jan;32(1):333-341. doi: 10.1245/s10434-024-16387-2. Epub 2024 Oct 21.
The prognosis remains poor for stage III gastric cancer, and neoadjuvant chemotherapy is increasingly used to improve outcomes. Accurate diagnosis prior to treatment is essential to develop appropriate treatment strategies for poor prognosis subgroups. This study aims to enhance the accuracy of pre-treatment gastric cancer diagnosis using a biological approach centered on circulating circular RNA (circRNA).
We conducted a comprehensive analysis of circRNA expression profiles using two Gene Expression Omnibus datasets to identify circRNA candidates associated with stage III gastric cancer. Subsequently, we validated these circRNA biomarkers in two independent clinical cohorts comprising a total of 174 patients with gastric cancer and non-disease controls through real-time polymerase chain reaction (PCR).
Genome-wide circRNA analysis identified a panel of four biomarkers capable of diagnosing pathologically confirmed stage III (pStage III) gastric cancer. In a training cohort (n = 83), a clinically applicable panel of four circRNAs was developed (AUC 0.81), which was successfully validated in an independent clinical cohort (n = 82; AUC 0.76). To assess clinical utility, we combined clinical imaging (cStage) with the circRNA panel. Among those initially diagnosed as cStage III but later confirmed as pStage I/II, 86% were accurately diagnosed using the molecular biological approach with circRNAs.
We have developed a circRNA-based non-invasive liquid biopsy that can improve the diagnostic performance of pStage III gastric cancer before treatment. Our circRNA model could provide a sophisticated and personalized approach to assist in treatment planning for patients with advanced gastric cancer.
III期胃癌的预后仍然很差，新辅助化疗越来越多地用于改善治疗结果。治疗前的准确诊断对于为预后不良亚组制定合适的治疗策略至关重要。本研究旨在以循环环状RNA（circRNA）为中心，通过生物学方法提高治疗前胃癌诊断的准确性。
我们使用两个基因表达综合数据集对circRNA表达谱进行了全面分析，以鉴定与III期胃癌相关的circRNA候选物。随后，我们通过实时聚合酶链反应（PCR）在两个独立的临床队列中验证了这些circRNA生物标志物，这两个队列共有174例胃癌患者和非疾病对照。
全基因组circRNA分析确定了一组能够诊断病理证实的III期（pStage III）胃癌的四种生物标志物。在一个训练队列（n = 83）中，开发了一个临床上适用的由四种circRNA组成的检测组（AUC 0.81），并在一个独立的临床队列（n = 82；AUC 0.76）中成功验证。为了评估临床实用性，我们将临床影像学（cStage）与circRNA检测组相结合。在那些最初被诊断为cStage III但后来被证实为pStage I/II的患者中，86% 使用基于circRNA的分子生物学方法被准确诊断。
我们开发了一种基于circRNA的非侵入性液体活检方法，可提高治疗前pStage III胃癌的诊断性能。我们的circRNA模型可以提供一种精细且个性化的方法，以协助晚期胃癌患者的治疗规划。
