Mitochondrial Common Deletion, a Potential Biomarker for Cancer Occurrence, Is Selected against in Cancer Background: A Meta-Analysis of 38 Studies

Abstract

Mitochondrial dysfunction has been long proposed to play a major role in tumorigenesis. Mitochondrial DNA (mtDNA) mutations, especially the mtDNA 4,977 bp deletion has been found in patients of various types of cancer. In order to comprehend the mtDNA 4,977 bp deletion status in various cancer types, we performed a meta-analysis composed of 33 publications, in which a total of 1613 cancer cases, 1516 adjacent normals and 638 healthy controls were included. When all studies were pooled, we found that cancerous tissue carried a lower mtDNA 4,977 bp deletion frequency than adjacent non-cancerous tissue (OR = 0.43, 95% CI = 0.20–0.92, P = 0.03 for heterogeneity test, I2 = 91.5%) among various types of cancer. In the stratified analysis by cancer type the deletion frequency was even lower in tumor tissue than in adjacent normal tissue of breast cancer (OR = 0.19, 95% CI = 0.06–0.61, P = 0.005 for heterogeneity test, I2 = 82.7%). Interestingly, this observation became more significant in the stratified studies with larger sample sizes (OR = 0.70, 95% CI = 0.58–0.86, P = 0.0005 for heterogeneity test, I2 = 95.1%). Furthermore, when compared with the normal tissue from the matched healthy controls, increased deletion frequencies were observed in both adjacent non-cancerous tissue (OR = 3.02, 95% CI = 2.13–4.28, P<0.00001 for heterogeneity test, I2 = 53.7%), and cancerous tissue (OR = 1.36, 95% CI = 1.04–1.77, P = 0.02 for heterogeneity test, I2 = 83.5%). This meta-analysis suggests that the mtDNA 4,977 bp deletion is often found in cancerous tissue and thus has the potential to be a biomarker for cancer occurrence in the tissue, but at the same time being selected against in various types of carcinoma tissues. Larger and better-designed studies are still warranted to confirm these findings.

Mitochondrial common deletion is elevated in blood of breast cancer patients mediated by oxidative stress

“…Multiple reports have associated the occurrence of this mtDNA common deletion with a wide range of cancer types including breast cancer (Lu et al, 2009; Nie et al, 2013). Investigations involving cell lines further implicated the common deletion in apoptosis and tumorigenesis (Lee et al, 2007; Wang and Lu, 2009).…”

“…In addition, increasing evidence suggests that mitochondrial function is severely impaired in various cancers including breast cancer (Deus et al, 2014; Neuzil and Moreno-Sanchez, 2013) due to genetic defects in the OXPHOS system (Chandra and Singh, 2011). Consequently, mtDNA mutations have been recognized as an important aspect of breast cancer occurrence and development (Nie et al, 2013; Shen et al, 2010; Shen et al, 2011; Yu et al, 2009). …”

D-loop somatic mutations and ∼5 kb “common” deletion in mitochondrial DNA: important molecular markers to distinguish oral precancer and cancer

“…In studies on other cancers [25,27], ∼5 kb deletion was found to be consistently lowered in cancer tissues; this deletion was detected in 24 % of the breast tumors, 52 % of the colorectal tumors, 79 % of the gastric tumors, and 40 % of the head and neck tumors as compared with 77, 83, 100, and 90 % of the adjacent respective non-tumor tissues [36]. In a meta-analysis on different cancers, ∼5 kb deletion was found to be less in cancer tissues compared to adjacent or matched normal tissues [37]. In another study on oral cancer and precancer tissues, not only this specific deletion was found to be lower in cancer tissues; a trend was observed in this lowering from controls to precancers to cancerous tissues [26].…”

Understanding Mitochondrial DNA in Brain Tumorigenesis

“…There is considerable evidence suggesting that mitochondria may serve as potential contributors to carcinogenesis even though the exact mechanism of how mitochondria involved is still debatable and is not welldocumented. Thus, mtDNA is now being targeted organelle by an increasing number of laboratories in order to investigate its potential role as biomarker for tumorigenesis in various types of tissues [86,87].…”