Mitochondrial DNA Copy Number in Egyptian Patients with Hepatitis C Virus-Related Hepatocellular Carcinoma

Hashad, Doaa; Elyamany, Amany; Salem, Perihan

doi:10.1089/gtmb.2015.0132

Cited by 12 publications

(11 citation statements)

References 37 publications

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“…Our analysis included 36 studies that focused on diverse cancer types from different origins around the world 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 . To reduce the uncertainty induced by confusing factors in the meta-analysis, we evaluated the association between mtDNA content with cancer risk in an overall analysis, as well as stratified analyses by cancer types, genders, ages, ethnicity and life styles.…”

Section: Discussionmentioning

confidence: 99%

Altered mitochondrial DNA copy number contributes to human cancer risk: evidence from an updated meta-analysis

Yao

Shen

2016

Sci Rep

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Accumulating epidemiological evidence indicates that the quantitative changes in human mitochondrial DNA (mtDNA) copy number could affect the genetic susceptibility of malignancies in a tumor-specific manner, but the results are still elusive. To provide a more precise estimation on the association between mtDNA copy number and risk of diverse malignancies, a meta-analysis was conducted by calculating the pooled odds ratios (OR) and the 95% confidence intervals (95% CI). A total of 36 case-control studies involving 11,847 cases and 15,438 controls were finally included in the meta-analysis. Overall analysis of all studies suggested no significant association between mtDNA content and cancer risk (OR = 1.044, 95% CI = 0.866–1.260, P = 0.651). Subgroup analyses by cancer types showed an obvious positive association between mtDNA content and lymphoma and breast cancer (OR = 1.645, 95% CI = 1.117–2.421, P = 0.012; OR = 1.721, 95% CI = 1.130–2.622, P = 0.011, respectively), and a negative association for hepatic carcinoma. Stratified analyses by other confounding factors also found increased cancer risk in people with drinking addiction. Further analysis using studies of quartiles found that populations with the highest mtDNA content may be under more obvious risk of melanoma and that Western populations were more susceptible than Asians.

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Section: Discussionmentioning

confidence: 99%

Altered mitochondrial DNA copy number contributes to human cancer risk: evidence from an updated meta-analysis

Yao

Shen

2016

Sci Rep

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“…In this study, we for the first time identified leukocyte mtDNA content as an independent prognostic factor for HCC, indicating that high leukocyte mtDNA content was associated with poor OS and RFS of patients. In comparison, Hashad et al have reported that HCV-related HCC patients with multicentric hepatic lesions have significantly lower mtDNA content than those with less advanced disease, suggesting that functional roles of mtDNA copy number may be disease-specific [16]. Collectively, these findings support the point of view that mtDNA content variations are involved in the progression of cancer, although the molecular mechanisms underlying the regulation of mtDNA copy number, especially in lymphocytes from cancer patients, remains to be largely unclear.…”

Section: Discussionmentioning

confidence: 99%

“…Yamada et al have found that HCC tissues have a reduced copy number of mtDNA when compared with paired non-tumor tissues, which is associated with malignant potential of HCC [15]. In recent years, there are a series of reports on the association of the mtDNA content in peripheral blood lymphocytes (PBLs) with cancer susceptibility [16–20]. However, only two studies have indicated that mtDNA content in PBLs is associated with breast cancer progression and CRC prognosis [21, 22].…”

Section: Introductionmentioning

confidence: 99%

High leukocyte mtDNA content contributes to poor prognosis through ROS-mediated immunosuppression in hepatocellular carcinoma patients

Zhou

et al. 2016

Oncotarget

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Compelling epidemiological evidences indicate a significant association between leukocyte mitochondrial DNA (mtDNA) content and incidence risk of several malignancies, including hepatocellular carcinoma (HCC). However, whether leukocyte mtDNA content affect prognosis of HCC patients and underlying mechanism has never been explored. In our study, leukocyte mtDNA content was measured in 618 HCC patients and its prognostic value was analyzed. Moreover, we detected the immunophenotypes of peripheral blood mononuclear cells (PBMCs) and plasma concentrations of several cytokines in 40 HCC patients and assessed the modulating effects of mtDNA content on immunosuppression in cell models. Our results showed that HCC patients with high leukocyte mtDNA content exhibited a significantly worse recurrence-free survival (RFS) and overall survival (OS) than those with low leukocyte mtDNA content. Leukocyte mtDNA content and TNM stage exhibited a notable joint effect in prognosis prediction. Furthermore, we found that patients with high leukocyte mtDNA content exhibited a higher frequency of CD4+CD25+FOXP3+ regulatory T (Treg) cells and lower frequency of NK cells in PBMCs and had higher TGF-β1 and lower TNF-α and IFN-γ plasma concentration when compared with those with low leukocyte mtDNA content, which suggests an immunosuppressive status. High leukocyte mtDNA content significantly enhanced the ROS-mediated secretion of TGF-β1, which accounted for higher Treg and lower NK frequency in PBMCs. In a conclusion, our study for the first time demonstrates that leukocyte mtDNA content is an independent prognostic marker complementing TNM stage and associated with an ROS-mediated immunosuppressive phenotype in HCC patients.

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“…A study suggested that mtDNA content analysis from peripheral blood could serve as a noninvasive biomarker and predictor for hepatocellular carcinoma risk in patients with hepatitis C [152]. Supported by other authors, their study used plasma and found it as a promising complementary sample alongside tissue specimens that served as a predictor for diagnosis and prognosis of lung cancer [154].…”

Section: Circulatingmentioning

confidence: 98%

“…Naturally alike, vigorous researches were conducted to find the potential link between cf-mtDNA and various cancers. cf-mtDNA is much more preferable as a noninvasive biomarker with easier sampling procedures and handling during molecular analysis [19,102,108,135,136,140,152,153].…”

Section: Circulatingmentioning

confidence: 99%

The Uprising of Mitochondrial DNA Biomarker in Cancer

2021

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Cancer is a heterogeneous group of diseases, the progression of which demands an accumulation of genetic mutations and epigenetic alterations of the human nuclear genome or possibly in the mitochondrial genome as well. Despite modern diagnostic and therapeutic approaches to battle cancer, there are still serious concerns about the increase in death from cancer globally. Recently, a growing number of researchers have extensively focused on the burgeoning area of biomarkers development research, especially in noninvasive early cancer detection. Intergenomic cross talk has triggered researchers to expand their studies from nuclear genome-based cancer researches, shifting into the mitochondria-mediated associations with carcinogenesis. Thus, it leads to the discoveries of established and potential mitochondrial biomarkers with high specificity and sensitivity. The research field of mitochondrial DNA (mtDNA) biomarkers has the great potential to confer vast benefits for cancer therapeutics and patients in the future. This review seeks to summarize the comprehensive insights of nuclear genome cancer biomarkers and their usage in clinical practices, the intergenomic cross talk researches that linked mitochondrial dysfunction to carcinogenesis, and the current progress of mitochondrial cancer biomarker studies and development.

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Mitochondrial DNA Copy Number in Egyptian Patients with Hepatitis C Virus-Related Hepatocellular Carcinoma

Cited by 12 publications

References 37 publications

Altered mitochondrial DNA copy number contributes to human cancer risk: evidence from an updated meta-analysis

Altered mitochondrial DNA copy number contributes to human cancer risk: evidence from an updated meta-analysis

High leukocyte mtDNA content contributes to poor prognosis through ROS-mediated immunosuppression in hepatocellular carcinoma patients

The Uprising of Mitochondrial DNA Biomarker in Cancer

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