我们的目的是确定接受内镜粘膜下剥离术 (ESD) 治疗的早期胃癌 (EGC) 患者中异时性胃癌 (MGC) 的预测标志物。对接受 ESD 的 EGC 患者的非癌性胃粘膜样本进行批量 RNA 测序在最初 EGC 诊断时。其中包括 23 名发生 MGC 的患者，以及 23 名 3 年以上没有其他胃肿瘤的对照患者（按年龄、性别和幽门螺杆菌感染状态 1:1 匹配）。鉴定了候选差异表达基因，使用实时定量聚合酶链反应和使用胃细胞系的细胞活力测定从中选择生物标志物。由 55 名 MGC 患者和 125 名对照组成的独立验证队列用于标记物验证。我们还在初步诊断时检查了胃肠化生（一种已知的癌前病变）的严重程度。从发现队列中鉴定出 86 个候选基因，其中 KDF1 和 CDK1 被选为 MGC 标记物，并在验证队列中得到证实。 CERB5 和 AKT2 亚型被确定为与肠上皮化生相关的标志物，与对照组相比，在 MGC 患者中也高度表达 (p < 0.01)。将这些标志物与临床数据（年龄、性别、幽门螺杆菌和肠上皮化生的严重程度）相结合，得出 MGC 预测的曲线下面积 (AUC) 为 0.91 (95% CI，0.85-0.97)。 评估非癌性生物标志物胃粘膜可能是预测 EGC 患者 MGC 和识别发生 MGC 风险较高的患者的有用方法，这些患者可以从严格的监测中受益。© 2024 作者。约翰·威利出版的癌症医学

We aimed to identify predictive markers for metachronous gastric cancer (MGC) in early gastric cancer (EGC) patients curatively treated with endoscopic submucosal dissection (ESD).From EGC patients who underwent ESD, bulk RNA sequencing was performed on non-cancerous gastric mucosa samples at the time of initial EGC diagnosis. This included 23 patients who developed MGC, and 23 control patients without additional gastric neoplasms for over 3 years (1:1 matched by age, sex, and Helicobacter pylori infection state). Candidate differentially-expressed genes were identified, from which biomarkers were selected using real-time quantitative polymerase chain reaction and cell viability assays using gastric cell lines. An independent validation cohort of 55 MGC patients and 125 controls was used for marker validation. We also examined the severity of gastric intestinal metaplasia, a known premalignant condition, at initial diagnosis.From the discovery cohort, 86 candidate genes were identified of which KDF1 and CDK1 were selected as markers for MGC, which were confirmed in the validation cohort. CERB5 and AKT2 isoform were identified as markers related to intestinal metaplasia and were also highly expressed in MGC patients compared to controls (p < 0.01). Combining these markers with clinical data (age, sex, H. pylori and severity of intestinal metaplasia) yielded an area under the curve (AUC) of 0.91 (95% CI, 0.85-0.97) for MGC prediction.Assessing biomarkers in non-cancerous gastric mucosa may be a useful method for predicting MGC in EGC patients and identifying patients with a higher risk of developing MGC, who can benefit from rigorous surveillance.© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.