Yu Yingdian, Xue Wenyuan, Liu Zefeng, Chen Shang, Wang Jun, Peng Quanzhou, Xu Linhao, Liu Xin, Cui Chunhui, Fan Jian-Bing
Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China.
Department of General Surgery, Zhujiang Hosipital, Southern Medical University, Guangzhou, China.
Front Oncol. 2022 Oct 14;12:1000823. doi: 10.3389/fonc.2022.1000823. eCollection 2022.
Lymph node metastasis (LNM) of colorectal cancer (CRC) is an important factor for both prognosis and treatment. Given the deficiencies of conventional tests, we aim to discover novel DNA methylation markers to efficiently identify LNM status of CRC. In this study, genome-wide methylation sequencing was performed in a cohort (n=30) using fresh CRC tissue to discover differentially methylated markers. These markers were subsequently validated with fluorescence quantitative PCR in a cohort (n=221), and the optimal marker was compared to conventional diagnostic methods. Meanwhile, immunohistochemistry was used to verify the effectiveness of the antibody corresponding to this marker in a cohort (n=56). achieved an AUC of 0.87, specificity of 87.3%, sensitivity of 75.7%, and accuracy of 81.9%, which outperformed conventional methods including imaging (CT, PET-CT) with an AUC of 0.52, CA199 with an AUC of 0.58, CEA with an AUC of 0.56. was also superior to clinicopathological indicators including the depth of tumor invasion and lymphatic invasion with an AUC of 0.61and 0.63 respectively. Moreover, the AUC of antibody was 0.84, which was also better than these conventional methods. In conclusion, A novel methylation marker could be used as a simple, cost-effective, and reliable diagnostic method for LNM of CRC.
结直肠癌(CRC)的淋巴结转移(LNM)是影响预后和治疗的重要因素。鉴于传统检测方法存在不足,我们旨在发现新的DNA甲基化标志物,以有效识别CRC的LNM状态。在本研究中,对一组(n = 30)使用新鲜CRC组织进行全基因组甲基化测序,以发现差异甲基化标志物。随后在一组(n = 221)中用荧光定量PCR验证这些标志物,并将最佳标志物与传统诊断方法进行比较。同时,在一组(n = 56)中使用免疫组织化学验证与该标志物对应的抗体的有效性。其曲线下面积(AUC)为0.87,特异性为87.3%,灵敏度为75.7%,准确性为81.9%,优于包括成像检查(CT、PET-CT)(AUC为0.52)、CA199(AUC为0.58)、癌胚抗原(CEA)(AUC为0.56)等传统方法。它也优于包括肿瘤浸润深度和淋巴浸润等临床病理指标,其AUC分别为0.61和0.63。此外,该抗体的AUC为0.84,也优于这些传统方法。总之,一种新的甲基化标志物可作为一种简单、经济高效且可靠的CRC-LNM诊断方法。