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

Abstract

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.

Mitochondrial DNA copy number is associated with all‐cause mortality and cardiovascular events in patients with peripheral arterial disease

“…Recent data revealed that tumour cells of many types of cancer have fewer copies of mitochondrial DNA than the cells that make up normal tissue . On the other hand, mtDNA copies can be released into the circulation from damaged or disintegrating tumour cells and might result in a preponderance of mtDNA‐CN when these copies are measured only in cell‐free DNA . As we discussed recently , the measurement of mtDNA copy numbers from nuclear cells as done in our study is an attempt to assess relative mitochondrial abundance within cells, and therefore a higher mtDNA copy number is expected to be associated with beneficial outcomes as observed in the present study.…”

“…However, the risk was more than threefold increased in the lowest quartile of mtDNA‐CN. Currently, contrary information on the association between mtDNA‐CN and cancer can be found in the literature reporting decreased as well as increased mtDNA‐CN in patients with cancer . One of the reasons for these diverging results might be whether these measurements are done in the tumour tissue, peripheral blood mononuclear cells or whole blood or from cell‐free circulating mtDNA.…”

“…Other studies in patients with end‐stage kidney disease reported conflicting results . The studies on mtDNA‐CN and cancer are quite heterogeneous depending on cancer type and the source of cells investigated .…”

<p>Pathogenic Heteroplasmic Somatic Mitochondrial DNA Mutation Confers Platinum-Resistance and Recurrence of High-Grade Serous Ovarian Cancer</p>

“… 11 , 19 , 20 Multiple studies have indicated that some germline polymorphisms in mtDNA d-loop region may be related to an increased risk of the malignancies. 21 , 22 Cancer cells are very different from normal cells, and they use aerobic glycolysis, called warburg effect, to generate energy and metabolic intermediates for the rapid proliferation and aggressiveness. 23 A series of studies suggested that some pathogenic somatic mtDNA mutations of cancer cells can confer cancerogenesis, and promote aggressiveness in vitro and in vivo by changing mitochondrial metabolism, and activating anti-apoptotic and oncogenic signaling pathways.…”

Role of intestinal flora in colorectal cancer from the metabolite perspective: a systematic review

“… 30 Finally, mitochondria are the key location for carbohydrate metabolism, and mitochondrial dysfunction is one the most important features in colorectal cancer and intestinal flora imbalance. 31 , 32 …”