Shanghai National Engineering Research Center for Biochip at Shanghai and Shanghai Biochip Limited Corporation, Shanghai, China; Department of Pathology, Shanghai Tongji Hospital, Tongji Hospital Affiliated to Tongji University, Shanghai, China.
Shanghai National Engineering Research Center for Biochip at Shanghai and Shanghai Biochip Limited Corporation, Shanghai, China.
Bosn J Basic Med Sci. 2021 Oct 1;21(5):577-586. doi: 10.17305/bjbms.2021.5576.
Liquid biopsy represents a diagnostic and monitoring tool and the circulating cell-free mitochondrial DNA (mtDNA) plays a vital role in tumor diagnosis and dynamic assessment. Colorectal cancer (CRC) is one of the most common fatal cancers worldwide. Mitochondrially encoded NADH dehydrogenase subunit 1 (MT-ND1) encodes the biggest subunit of respiratory complex I of mtDNA, and mutations in the MT-ND1 are common in CRC. We sought to determine if mutations in circulating MT-ND1 could be a potential biomarker for colorectal cancer. In this study, twenty-two CRC patients at Zhujiang Hospital were included. We mainly used droplet digital PCR to determine the mutation status of MT-ND1, combined with clinical data. In the experiment in vivo, cell-free mtDNA generally presented high concordance with tumor tissues. By quantitative PCR, the MT-ND1 content of plasma in CRC patients was significantly higher than that in healthy individuals (58.01 vs. 0.64, p=0.027). The detection of circulating MT-ND1 content and variants (m.3606 A>G, m.3970 C>T, m.4071 C>T, m.4086 C>T) in cfDNA showed a good correlation with predicted tumor response and progression to chemotherapy. In conclusion, the content and variants of circulating MT-ND1 may become a versatile tool for the diagnosis and monitoring of colorectal cancer.
液体活检是一种诊断和监测工具，循环无细胞线粒体 DNA（mtDNA）在肿瘤诊断和动态评估中起着至关重要的作用。结直肠癌（CRC）是全球最常见的致命癌症之一。线粒体编码的烟酰胺腺嘌呤二核苷酸脱氢酶亚单位 1（MT-ND1）编码 mtDNA 呼吸复合物 I 的最大亚基，MT-ND1 中的突变在 CRC 中很常见。我们试图确定循环 MT-ND1 中的突变是否可以成为结直肠癌的潜在生物标志物。在这项研究中，纳入了珠江医院的 22 名 CRC 患者。我们主要使用液滴数字 PCR 来确定 MT-ND1 的突变状态，并结合临床数据。在体内实验中，无细胞 mtDNA 通常与肿瘤组织高度一致。通过定量 PCR，CRC 患者血浆中的 MT-ND1 含量明显高于健康个体（58.01 与 0.64，p=0.027）。循环 MT-ND1 含量和变体（m.3606 A>G、m.3970 C>T、m.4071 C>T、m.4086 C>T）在 cfDNA 中的检测与预测的肿瘤反应和化疗进展具有良好的相关性。总之，循环 MT-ND1 的含量和变体可能成为诊断和监测结直肠癌的多功能工具。
