Mitochondrial DNA haplogroup M7: A predictor of poor prognosis for colorectal cancer patients in Chinese population. Issue 3 (7th December 2022)

• Record Type: Journal Article
• Authors: Yan, Zeyu; Yuan, Qing; He, Yiwei; Peng, Fan; Liu, Yang; Zhang, Huanqin; Ji, Xiaoying; He, Xianli; Zhao, Qi; Xing, Jinliang; Guo, Xu
• Is Part Of: Cancer science. Volume 114:Issue 3(2023)
• Page Start: 1056
• Page End: 1066
• Publication Date: 2022-12-07
• Subjects: colorectal cancer -- haplogroup -- mitochondrial DNA -- prognosis -- single‐nucleotide polymorphisms; Cancer -- Periodicals; Neoplasms -- Periodicals; Research -- Periodicals; Electronic journals; 616.994005
• DOI: 10.1111/cas.15654
• Languages: English
• ISSNs: 1347-9032

Abstract

Abstract: Haplogroups and single‐nucleotide polymorphisms (SNP) of mitochondrial DNA (mtDNA) were associated with the prognosis of many types of cancer patients. However, whether mtDNA haplogroups contribute to clinical outcomes of colorectal cancer (CRC) in Chinese population remains to be determined. In this study, mtDNA of tissue samples from 445 CRC patients from Northwestern China was sequenced to evaluate the association between haplogroup and prognosis. The mtDNA sequencing data of 1015 CRC patients from Southern China were collected for validation. We found patients with mtDNA haplogroup M7 had a significantly higher death risk when compared with patients with other haplogroups in both Northwestern (Hazard ratio [HR] = 3.093, 95% CI = 1.768–5.411, p < 0.001) and Southern (HR = 1.607, 95% CI = 1.050–2.459, p = 0.029) China. Then, a haplogroup M7–based mtSNP classifier was selected by using LASSO Cox regression analysis. A nomogram comprising the mtSNP classifier and clinicopathological variables was developed to predict the prognosis of CRC patients (area under the curve [AUC] 0.735, 95% CI = 0.679–0.791). Furthermore, patients with high‐ and low‐risk scores calculated by the haplogroup M7–based mtSNP classifier exhibited significantly different overall survival (OS) and recurrence‐free survival (RFS) (all p < 0.001). Finally, RNA‐seq and immunohistochemical analyses indicated the poor prognosis of patients with haplogroup M7 may be related to mitochondrial dysfunction and immune abnormalities in CRC tissues. In conclusion, the haplogroup M7 and haplogroup M7–based mtSNP classifier seems to be a practical and reliable prognostic predictor for CRC patients, which provides a potential tool of clinical decision‐making for patients with haplogroup M7 in Chinese population. Abstract : Haplogroup M7 is associated with poor outcomes in Chinese colorectal cancer (CRC) patients. The poor prognosis may be related to mitochondrial dysfunction and immune abnormalities. We developed a practical and reliable prognostic predictor based on haplogroup M7–related mtSNPs for CRC patients, which provides a potential tool of clinical decision‐making for patients with haplogroup M7 in Chinese population.