SFRP2和RPRM作为基于甲基化的血清生物标志物用于胃癌检测。

SFRP2 and RPRM as methylation based serum biomarkers for the detection of gastric cancer.

作者信息

Dede Serap, Şakalar Çağrı, Yılmaz Barış, Çubukcı Gamze, Acar Muradiye, Yavuz Aydın, Aksu Gizem, Altıner Saygın, Yüksel Osman, Ayaz Furkan, Aydemir Esra

机构信息

Eryiğit Medical Devices R&D Center, Ankara, Turkey.

Department of Molecular and Medical Genetics, School of Engineering and Natural Sciences, Biruni University, Istanbul, Turkey.

出版信息

Discov Oncol. 2025 Aug 24;16(1):1606. doi: 10.1007/s12672-025-03472-5.

DOI:10.1007/s12672-025-03472-5

PMID:40849852

Abstract

BACKGROUND

Gastric cancer (GC) has a high mortality rate due to the diagnosis in advanced stages. Aberrant DNA methylation is the earliest event in carcinogenesis and can be noninvasively detected in cell-free DNA (cfDNA) from gastric cancer patients.

METHODS

A total of 143 serum samples were analyzed, including 33 GC patients, 30 chronic gastritis (ChG) patients, and 80 healthy individuals. Additionally, tissue samples were collected from 30 GC patients (stages I-IV) and 38 ChG patients. Methylation patterns of ten genes were examined in GC cells, as well as in serum and tissue samples from GC, ChG, and control groups using methylation-specific qPCR. Statistical evaluations were conducted on various parameters including Ct differences, categorical variables, sensitivity, and specificity.

RESULTS

APC, CDH1, RASSF1A, hMLH1, RUNX3, p16, SFRP2, RNF180, PCDH10, and RPRM were all significantly hypermethylated in the tissues of GC patients compared to those with ChG (P < 0.001). SFRP2, RPRM, APC, PCDH10, and RNF180 genes were analyzed in sera of 3 groups. Among them, SFRP2 methylation was detected in 71.87% of GC, 16.6% of ChG and 8.8% of the control group. The methylation frequencies of RPRM were 66.6% in GC, 13.3% in ChG, and 7.5% in the control group. In a dual-gene panel assay combining SFRP2 and RPRM, the sensitivity and specificity for detecting gastric cancer in serum samples were 57.58% and 96.25%, respectively, when comparing the cancer and control groups. The sensitivity was 78.79%, the specificity was 90.00% and AUC was 0.931 for GC and control groups (P < 0.0001). The sensitivity was 78.79%, the specificity was 83.33% and AUC was 0.879 for the discrimination of GC and ChG (P < 0.0001).

CONCLUSIONS

Methylation of 10 genes were studied and a prototype early diagnosis tool for GC utilizing SFRP2 and RPRM with high sensitivity and specificity was developed.

摘要

背景

由于胃癌（GC）多在晚期被诊断出来，其死亡率很高。异常DNA甲基化是致癌过程中最早出现的事件，并且可以在胃癌患者的游离DNA（cfDNA）中进行无创检测。

方法

共分析了143份血清样本，包括33例胃癌患者、30例慢性胃炎（ChG）患者和80例健康个体。此外，还收集了30例胃癌患者（I-IV期）和38例慢性胃炎患者的组织样本。使用甲基化特异性定量PCR检测了GC细胞以及GC、ChG和对照组血清和组织样本中10个基因的甲基化模式。对包括Ct差异、分类变量、敏感性和特异性等各种参数进行了统计评估。

结果

与慢性胃炎患者相比，胃癌患者组织中APC、CDH1、RASSF1A、hMLH1、RUNX3、p16、SFRP2、RNF180、PCDH10和RPRM均显著高甲基化（P < 0.001）。对3组患者的血清分析了SFRP2、RPRM、APC、PCDH10和RNF180基因。其中，71.87%的胃癌患者、16.6%的慢性胃炎患者和8.8%的对照组患者检测到SFRP2甲基化。RPRM的甲基化频率在胃癌患者中为66.6%，在慢性胃炎患者中为13.3%，在对照组中为7.5%。在结合SFRP2和RPRM的双基因检测中，比较癌症组和对照组时，血清样本中检测胃癌的敏感性和特异性分别为57.58%和96.25%。对于胃癌组和对照组，敏感性为78.79%，特异性为90.00%，AUC为0.931（P < 0.0001）。对于区分胃癌和慢性胃炎，敏感性为78.79%，特异性为83.33%，AUC为0.879（P < 0.0001）。