Abstract
Previous studies have suggested that mitochondrial DNA (mtDNA) copy number was associated with cancer risk. However, no solid conclusion revealed the potential predictive value of mtDNA copy number for cancer prognosis. The present meta-analysis was performed to clarify the problem. Hence, we performed a systematic search in PubMed, EmBase, Web of Science databases independently and a total of eighteen studies comprising 3961 cases satisfied the criteria and finally enrolled. Our results didn’t show the association between them but significant heterogeneity in overall analysis (OS: HR = 0.923, 95% CI: 0.653–1.306, p = 0.652; DFS: HR = 0.997, 95% CI: 0.599–1.659, p = 0.99). However, subgroup analysis stratified by sample came to the opposite conclusion. High level mitochondrial DNA copy number in peripheral blood predicted a poor cancer prognosis (OS: HR = 1.624, 95% CI: 1.211–2.177, p = 0.001; DFS: HR = 1.582, 95% CI: 1.026–2.439, p = 0.038) while patients with high level mitochondrial DNA copy number in tumor tissue exhibited better outcomes (OS: HR = 0.604 95% CI: 0.406–0.899, p = 0.013; DFS: HR = 0.593, 95% CI: 0.411–0.857, p = 0.005). These findings were further proved in detailed analyses in blood or tissue subgroup. In conclusion, our study suggested the elevated mtDNA copy number in peripheral blood predicted a poor cancer prognosis while the better outcome was presented among patients with elevated mtDNA copy number in tumor tissue.
Highlights
Cancer is one of the leading causes of mortality all over the world[1]
Digestive system cancers were investigated in 10 studies (6 on colorectal cancer, 2 on gastric cancer, 2 on hepatocellular carcinoma) while 2 studies on breast cancer, 2 studies on glioma and 1 studies respectively on cervical cancer, head and neck cancer, laryngeal cancer and non-small cell lung cancer. 15 studies reported mitochondrial DNA copy number as dichotomous variables and 3 studies was divided into three categorical variables
In subgroup analysis by sample, the heterogeneity was to some extent decreased and we indicated that high level mitochondrial DNA copy number in peripheral blood predicted a poor cancer prognosis (HR = 1.624, 95% confidence interval (95% CI): 1.211–2.177, p = 0.001) while high level mitochondrial DNA copy number in tumor tissue was significantly associated with better overall survival in cancer patients (HR = 0.604 95% CI: 0.406–0.899, p = 0.013) (Fig. 2)
Summary
Cancer is one of the leading causes of mortality all over the world[1]. significant achievements have been made in the area of cancer therapy, the occurrence of cancer was still on the increase especially in developing countries, and the mortality rates remained high globally[1]. Much more attention has been paid to independently evaluate the prognostic value of mtDNA copy number in various cancer types, and the results are controversial, even in the studies on the same type of cancer like colorectal cancer[16,17,18]. It was timely and necessary to analyze globally the prognostic value of mtDNA copy number in larger population to fill the gap of lacking the related comprehensive analysis and clarify the pending issue. We performed a meta-analysis integrating the valid results from conditional homogeneous studies to quantitatively review the effect of high versus low mtDNA copy number on the survival of patients in peripheral blood and tissue with some specific types of cancer, respectively. We compared the predicting value of mtDNA in terms of origin of population and other characteristics through subgroup analysis
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