Is Mitochondrial DNA Copy Number Associated with Clinical Characteristics and Prognosis in Gastric Cancer?

Lee, Hyunsu; Lee, Jae-Ho; Kim, Dong-Choon; Hwang, Ilseon; Kang, Yuna; Gwon, Gi-Jeong; Choi, In‐Jang; Kim, Shin

doi:10.7314/apjcp.2015.16.1.87

Cited by 10 publications

(8 citation statements)

References 27 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%

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%

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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“…The clinicopathological significance of TL and mitochondrial genetic change has been previously studied in GC by a number of groups (11,12,14,21,22). TL was previously demonstrated to differ in GC according to Helicobacter pylori infection status, microsatellite instability (MSI), and non-steroidal anti-inflammatory drug use (26)(27)(28)(29).…”

Section: Discussionmentioning

confidence: 99%

“…Past reviews have emphasized the importance of the telomere-p53-mitochondrion axis for cancer, suggesting that this may be targeted in future cancer therapy (19,20). Our recent studies (21,22) have also investigated these genetic changes in GC; however, their association has yet to be studied in cancer tissue samples.…”

Section: Introductionmentioning

confidence: 99%

Telomere length is correlated with mitochondrial DNA copy number in intestinal, but not diffuse, gastric cancer

et al. 2017

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Abstract.A positive correlation between telomere length and mitochondrial DNA (mtDNA) copy number has previously been observed in healthy individuals, and in patients with psychiatric disorders. In the present study, telomere length and mtDNA copy number were evaluated in gastric cancer (GC) tissue samples. DNA was extracted from 109 GC samples (including 82 intestinal, and 27 diffuse cases), and the telomere length and mtDNA copy number were analyzed using a quantitative-polymerase chain reaction assay. The relative telomere length and mtDNA copy number in tumor tissue, as compared with in normal tissue, (mean ± standard deviation) in all GC samples were 11.48±1.14 and 14.86±1.35, respectively. Telomere length and mtDNA copy number were not identified as exhibiting clinical or prognostic value for GC. However, positive correlations between telomere length and mitochondrial DNA copy number were identified in GC (r=0.408, P<0.001) and in the adjacent normal mucosa (r=0.363; P<0.001). When stratified by Lauren classification, the correlation was identified in intestinal type GC samples (r=0.461; P<0.001), but not in diffuse type GC samples (r= 0.225; P= 0.260). This result indicated that loss of the correlation of telomeres and mitochondrial function may induce the initiation or progression of GC pathogenesis.

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“…Mitochondrial genome is also 10-20 times more susceptible to molecular alterations in comparison to nuclear genome [30]. This is mainly due to the mitochondrial physical proximity to OXPHOS (because accumulation of ROS may lead to mtDNA damage) and less effective repair mechanisms, including the absence of histones [1,31,32]. Indeed, unlike nDNA, mtDNA is not associated with histones, but these molecules are not "naked": they are present in areas called mt-nucleoids, associated with different proteins that contribute to mtDNA protection and stability.…”

Section: Mitochondrial Genomementioning

confidence: 99%

Mitochondrial Epigenetics: Non-Coding RNAs as a Novel Layer of Complexity

Cavalcante

Magalhães

Ribeiro-dos-Santos

et al. 2020

IJMS

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Mitochondria are organelles responsible for several functions involved in cellular balance, including energy generation and apoptosis. For decades now, it has been well-known that mitochondria have their own genetic material (mitochondrial DNA), which is different from nuclear DNA in many ways. More recently, studies indicated that, much like nuclear DNA, mitochondrial DNA is regulated by epigenetic factors, particularly DNA methylation and non-coding RNAs (ncRNAs). This field is now called mitoepigenetics. Additionally, it has also been established that nucleus and mitochondria are constantly communicating to each other to regulate different cellular pathways. However, little is known about the mechanisms underlying mitoepigenetics and nuclei–mitochondria communication, and also about the involvement of the ncRNAs in mitochondrial functions and related diseases. In this context, this review presents the state-of-the-art knowledge, focusing on ncRNAs as new players in mitoepigenetic regulation and discussing future perspectives of these fields.

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Is Mitochondrial DNA Copy Number Associated with Clinical Characteristics and Prognosis in Gastric Cancer?

Cited by 10 publications

References 27 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

Telomere length is correlated with mitochondrial DNA copy number in intestinal, but not diffuse, gastric cancer

Mitochondrial Epigenetics: Non-Coding RNAs as a Novel Layer of Complexity

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