High Copy Number of Mitochondrial DNA Predicts Poor Prognosis in Patients with Advanced Stage Colon Cancer

Wang, Yun; He, Shuixiang; Zhu, Xulong; Qiao, Wei; Zhang, Juan

doi:10.5301/jbm.5000211

Cited by 26 publications

(27 citation statements)

References 18 publications

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“…After a thorough review of titles and abstracts by two investigators independently, 394 studies were excluded and the full texts of remaining 26 references have also been artificial retrieved for further identification. Finally a total of 20 retrospective studies comprising 5413 patients were included in our study and 18 studies were used for analysis16171819202122252627282930313233343536. Among the included studies for analysis, there were 16 studies recruited Asian patients while 2 studies recruited Caucasian patients.…”

Section: Resultsmentioning

confidence: 99%

“…Among these factors, the qualitative and quantitative changes in nuclear or mitochondrial DNA have been frequently reported in human cancers262728293031, and the interplay between them may partly participate in the tumor-related process39. Previous studies have reported reduced levels of mtDNA transcripts and increased mtDNA copy number in brain and lung with ageing4041.…”

Section: Discussionmentioning

confidence: 99%

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Elevated Mitochondrial DNA Copy Number in Peripheral Blood and Tissue Predict the Opposite Outcome of Cancer: A Meta-Analysis

Chen

Wen

Sun

et al. 2016

Sci Rep

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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.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Elevated Mitochondrial DNA Copy Number in Peripheral Blood and Tissue Predict the Opposite Outcome of Cancer: A Meta-Analysis

Chen

Wen

Sun

et al. 2016

Sci Rep

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“…But it is known meanwhile that mtDNA content and OXPHOS activity do not always correspond well in tumor tissues and -more importantly- copy number studies sometimes did not even deliver homogenous results within a single entity. For example, in colorectal cancer one recent study observed a lower mtDNA copy number in colorectal carcinomas as compared to adenomas [95], while another publication described higher copy numbers in colorectal cancer tissues as compared to adjacent normal tissues and a positive association of high copy number with poor prognosis [96]. An increased mtDNA-level in gliomas was observed as compared to (not matched) normal brain tissues, high copy number being associated with better prognosis [97].…”

Section: Is Mtdna Copy Number Associated With Prognosis or General Camentioning

confidence: 99%

MtDNA As a Cancer Marker: A Finally Closed Chapter?

Kirches

2017

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Sequence alterations of the mitochondrial DNA (mtDNA) have been identified in many tu-mor types. Their nature is not entirely clear. Somatic mutation or shifts of heteroplasmic mtDNA vari-ants may play a role. These sequence alterations exhibit a sufficient frequency in all tumor types investi-gated thus far to justify their use as a tumor marker. This statement is supported by the high copy num-ber of mtDNA, which facilitates the detection of aberrant tumor-derived DNA in bodily fluids. This will be of special interest in tumors, which release a relatively high number of cells into bodily fluids, which are easily accessible, most strikingly in urinary bladder carcinoma. Due to the wide distribution of the observed base substitutions, deletions or insertions within the mitochondrial genome, high efforts for whole mtDNA sequencing (16.5 kb) from bodily fluids would be required, if the method would be in-tended for initial tumor screening. However, the usage of mtDNA for sensitive surveillance of known tumor diseases is a meaningful option, which may allow an improved non-invasive follow-up for the urinary bladder carcinoma, as compared to the currently existing cytological or molecular methods. Fol-lowing a short general introduction into mtDNA, this review demonstrates that the scenario of a sensi-tive cancer follow-up by mtDNA-analysis deserves more attention. It would be most important to inves-tigate precisely in the most relevant tumor types, if sequencing approaches in combination with simple PCR-assays for deletions/insertions in homopolymeric tracts has sufficient sensitivity to find most tu-mor-derived mtDNAs in bodily fluids.

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“…Wang et al supported that the mtDNA copy number increased in CRCs and it was a factor of poor prognosis [22]. The researches of Haja Mohideen et al suggested that mtDNA copy number both increased and decreased in CRCs and no association of the mtDNA copy number change with OS or DFS [23].…”

Section: Mtdna Copy Numbermentioning

confidence: 99%

Can Mitochondria DNA Provide a Novel Biomarker for Evaluating the Risk and Prognosis of Colorectal Cancer?

Han

Pan

2017

Disease Markers

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Colorectal cancer (CRC) was one of the most frequent cancers worldwide. Accurate risk and prognosis evaluation could obtain better quality of life and longer survival time for the patients. Current research hotspot was focus on the gene biomarker to evaluate the risk and prognosis. Mitochondrion contains its own DNA and regulates self-replicating so that it can be as a candidate biomarker for evaluating the risk and prognosis of colorectal cancer. But there were already huge controversies on this issue. The review was to summarize current viewpoints of the controversial issues and described our understanding from the four aspects including mtDNA copy number, mitochondrial displacement loop, mtDNA variation, and mtDNA microsatellite instability, wishing the summary of the mtDNA in colorectal cancer could provide a meaningful reference or a valuable direction in the future studies.

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High Copy Number of Mitochondrial DNA Predicts Poor Prognosis in Patients with Advanced Stage Colon Cancer

Abstract: High mtDNA content is a potential effective factor of poor prognosis in patients with advanced stage colon cancer.

Cited by 26 publications

References 18 publications

Elevated Mitochondrial DNA Copy Number in Peripheral Blood and Tissue Predict the Opposite Outcome of Cancer: A Meta-Analysis

Elevated Mitochondrial DNA Copy Number in Peripheral Blood and Tissue Predict the Opposite Outcome of Cancer: A Meta-Analysis

MtDNA As a Cancer Marker: A Finally Closed Chapter?

Can Mitochondria DNA Provide a Novel Biomarker for Evaluating the Risk and Prognosis of Colorectal Cancer?

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