目的:我们的目的是在内镜黏膜下剥离术(ESD)治疗的早期胃癌(EGC)患者中鉴定异时性胃癌(MGC)的预测标志物。
方法:来自接受ESD的EGC患者,在初次EGC诊断时,对非癌性胃粘膜样本进行大量RNA测序.这包括23名患有MGC的患者,和23名对照患者,没有额外的胃肿瘤超过3年(1:1匹配的年龄,性别,和幽门螺杆菌感染状态)。确定了候选的差异表达基因,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。55名MGC患者和125名对照的独立验证队列用于标记验证。我们还检查了胃肠上皮化生的严重程度,一种已知的癌前病变,在初步诊断。
结果:从发现队列中,确定了86个候选基因,其中选择KDF1和CDK1作为MGC的标记,这在验证队列中得到了证实。CERB5和AKT2同种型被鉴定为与肠上皮化生相关的标志物,并且与对照组相比,在MGC患者中也高表达(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)得出MGC预测的曲线下面积(AUC)为0.91(95%CI,0.85-0.97)。
结论:评估非癌性胃粘膜中的生物标志物可能是预测EGC患者中MGC和识别发生MGC风险较高的患者的有用方法,谁可以从严格的监控中受益。
OBJECTIVE: We aimed to identify predictive markers for metachronous gastric cancer (MGC) in early gastric cancer (EGC) patients curatively treated with endoscopic submucosal dissection (ESD).
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.