Enhancing Preoperative Diagnosis Accuracy of Stage III Gastric Cancer with Circulating circRNAs

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.