Quantitative detection of circulating MT-ND1 as a potential biomarker for colorectal cancer

Yichun Xu; Jiajing Zhou; Qing Yuan; Jun Su; Qian Li; Xiaoliang Lu; Liwen Zhang; Zhai Cai; Junsong Han

doi:10.17305/bjbms.2021.5576

Authors

Yichun Xu 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 https://orcid.org/0000-0002-7339-1693
Jiajing Zhou Shanghai National Engineering Research Center for Biochip at Shanghai and Shanghai Biochip Limited Corporation, Shanghai, China
Qing Yuan Shanghai National Engineering Research Center for Biochip at Shanghai and Shanghai Biochip Limited Corporation, Shanghai, China https://orcid.org/0000-0003-0297-854X
Jun Su Shanghai National Engineering Research Center for Biochip at Shanghai and Shanghai Biochip Limited Corporation, Shanghai, China 2Department of Pathology, Shanghai Tongji Hospital, Tongji Hospital Affiliated to Tongji University, Shanghai, China https://orcid.org/0000-0002-7509-4836
Qian Li Shanghai National Engineering Research Center for Biochip at Shanghai and Shanghai Biochip Limited Corporation, Shanghai, China 2Department of Pathology, Shanghai Tongji Hospital, Tongji Hospital Affiliated to Tongji University, Shanghai, China
Xiaoliang Lu Shanghai National Engineering Research Center for Biochip at Shanghai and Shanghai Biochip Limited Corporation, Shanghai, China https://orcid.org/0000-0003-1870-7314
Liwen Zhang Shanghai National Engineering Research Center for Biochip at Shanghai and Shanghai Biochip Limited Corporation, Shanghai, China 2Department of Pathology, Shanghai Tongji Hospital, Tongji Hospital Affiliated to Tongji University, Shanghai, China https://orcid.org/0000-0002-6304-0312
Zhai Cai Department of General Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, China
Junsong Han Shanghai National Engineering Research Center for Biochip at Shanghai and Shanghai Biochip Limited Corporation, Shanghai, China https://orcid.org/0000-0002-9405-9382

DOI:

https://doi.org/10.17305/bjbms.2021.5576

Keywords:

MT-ND1, colorectal cancer, mtDNA, cfDNA, biomarker

Abstract

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.