- Volume 16 Issue 1
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Is Mitochondrial DNA Copy Number Associated with Clinical Characteristics and Prognosis in Gastric Cancer?
- Lee, Hyunsu (Department of Anatomy, School of Medicine, Keimyung University) ;
- Lee, Jae-Ho (Department of Anatomy, School of Medicine, Keimyung University) ;
- Kim, Dong-Choon (Department of Internal Medicine, School of Medicine, Keimyung University) ;
- Hwang, IlSeon (Department of Pathology, School of Medicine, Keimyung University) ;
- Kang, Yu-Na (Department of Pathology, School of Medicine, Keimyung University) ;
- Gwon, Gi-Jeong (Department of Anatomy, School of Medicine, Keimyung University) ;
- Choi, In-Jang (Department of Anatomy, School of Medicine, Keimyung University) ;
- Kim, Shin (Department of Immunology, School of Medicine, Keimyung University)
- Published : 2015.02.04
Alterations in mitochondrial DNA (mtDNA) have been studied in various cancers. However, the clinical value of mtDNA copy number (mtCN) alterations in gastric cancer (GC) is poorly understood. In the present study, we investigated whether alterations in mtCNs might be associated with clinicopathological parameters in GC cases. mtCN was measured in 109 patients with GC by quantitative real-time PCR. Then, correlations with clinicopathological characteristics were analyzed. mtCN was elevated in 64.2% of GC tissues compared with paired, adjacent, non-cancerous tissue. However, the observed alterations in mtCN were not associated with any clinicopathological characteristics, including age, gender, TN stage, Lauren classification, lymph node metastasis, and depth of invasion. Moreover, Kaplan-Meier survival curves revealed that mtCN was not significantly associated with the survival of GC patients. In this study, we demonstrated that mtCN was not a significant marker for predicting clinical characteristics or prognosis in GC.
Supported by : National Research Foundation of Korea (NRF)
- Amuthan G, Biswas G, Zhang SY, et al (2001). Mitochondriato-nucleus stress signaling induces phenotypic changes, tumor progression and cell invasion. Embo J, 20, 1910-20. https://doi.org/10.1093/emboj/20.8.1910
- Bianchi NO, Bianchi MS, Richard SM (2001). Mitochondrial genome instability in human cancers. Mutat Res, 488, 9-23. https://doi.org/10.1016/S1383-5742(00)00063-6
- Cook CC, Higuchi M (2012). The awakening of an advanced malignant cancer: an insult to the mitochondrial genome. Biochim Biophys Acta, 1820, 652-62. https://doi.org/10.1016/j.bbagen.2011.08.017
- Correa P (1992). Human gastric carcinogenesis: a multistep and multifactorial process-first american cancer society award lecture on cancer epidemiology and prevention. Cancer Res, 52, 6735-40.
- Correa P, Shiao YH (1994). Phenotypic and genotypic events in gastric carcinogenesis. Cancer Res, 54, 1941-3.
- Cui H, Huang P, Wang Z, et al (2013). Association of decreased mitochondrial DNA content with the progression of colorectal cancer. BMC Cancer, 13, 110. https://doi.org/10.1186/1471-2407-13-110
- Dai J-G, Zhang Z-Y, Liu Q-X, Min J-X (2013). Mitochondrial genome microsatellite instability and copy number alteration in lung carcinomas. Asian Pac J Cancer Prev, 14, 2393-9. https://doi.org/10.7314/APJCP.2013.14.4.2393
- Guo W, Yang D, Xu H, et al (2013). Mutations in the D-loop region and increased copy number of mitochondrial DNA in human laryngeal squamous cell carcinoma. Mol Biol Rep, 40, 13-20. https://doi.org/10.1007/s11033-012-1939-7
- Howell N, Kubacka I, Mackey DA (1996). How rapidly does the human mitochondrial genome evolve? Am J Hum Genet, 59, 501-9.
- Jeong CW, Lee JH, Sohn SS, Ryu SW, Kim DK (2010). Mitochondrial microsatellite instability in gastric cancer and gastric epithelial dysplasia as a precancerous lesion. Cancer Epidemiol, 34, 323-7. https://doi.org/10.1016/j.canep.2010.03.015
- Lee HC, Li SH, Lin JC, et al (2004). Somatic mutations in the D-loop and decrease in the copy number of mitochondrial DNA in human hepatocellular carcinoma. Mutat Res, 547, 71-8. https://doi.org/10.1016/j.mrfmmm.2003.12.011
- Lee HC, Yin PH, Lu CY, Chi CW, Wei YH (2000). Increase of mitochondria and mitochondrial DNA in response to oxidative stress in human cells. Biochem J, 348, 425-32. https://doi.org/10.1042/0264-6021:3480425
- Lee JH, Ryu TY, Cho CH, Kim DK (2011). Different characteristics of mitochondrial microsatellite instability between uterine leiomyomas and leiomyosarcomas. Pathol Oncol Res, 17, 201-5. https://doi.org/10.1007/s12253-010-9297-z
- Liao LM, Baccarelli A, Shu XO, et al (2011). Mitochondrial DNA copy number and risk of gastric cancer: a report from the Shanghai women's health study. Cancer Epidemiol Biomarkers Prev, 20, 1944-9. https://doi.org/10.1158/1055-9965.EPI-11-0379
- Lievre A, Chapusot C, Bouvier AM, et al (2005). Clinical value of mitochondrial mutations in colorectal cancer. J Clin Oncol, 23, 3517-25. https://doi.org/10.1200/JCO.2005.07.044
- Lin CS, Wang LS, Tsai CM, Wei YH (2008). Low copy number and low oxidative damage of mitochondrial DNA are associated with tumor progression in lung cancer tissues after neoadjuvant chemotherapy. Interact Cardiovasc Thorac Surg, 7, 954-8. https://doi.org/10.1510/icvts.2008.177006
- Paabo S (1996). Mutational hot spots in the mitochondrial microcosm. Am J Hum Genet, 59, 493-6.
- Rugge M, Farinati F, Baffa R, et al (1994). Gastric epithelial dysplasia in the natural history of gastric cancer: a multicenter prospective follow-up study. interdisciplinary group on gastric epithelial dysplasia. Gastroenterology, 107, 1288-96. https://doi.org/10.1016/0016-5085(94)90529-0
- Savagner F, Franc B, Guyetant S, et al (2001). Defective mitochondrial ATP synthesis in oxyphilic thyroid tumors. J Clin Endocrinol Metab, 86, 4920-5. https://doi.org/10.1210/jcem.86.10.7894
- Shadel GS (2008). Expression and maintenance of mitochondrial DNA: new insights into human disease pathology. Am J Pathol, 172, 1445-56. https://doi.org/10.2353/ajpath.2008.071163
- Shadel GS, Clayton DA (1997). Mitochondrial DNA maintenance in vertebrates. Annu Rev Biochem, 66, 409-35. https://doi.org/10.1146/annurev.biochem.66.1.409
- Stoneking M (2000). Hypervariable sites in the mtDNA control region are mutational hotspots. Am J Hum Genet, 67, 1029-32. https://doi.org/10.1086/303092
- Wang Y, Liu VW, Ngan HY, Nagley P (2005). Frequent occurrence of mitochondrial microsatellite instability in the D-loop region of human cancers. Ann N Y Acad Sci, 1042, 123-9. https://doi.org/10.1196/annals.1338.012
- Wu CW, Yin PH, Hung WY, et al (2005). Mitochondrial DNA mutations and mitochondrial DNA depletion in gastric cancer. Genes Chromosomes Cancer, 44, 19-28. https://doi.org/10.1002/gcc.20213
- Yin PH, Lee HC, Chau GY, et al (2004). Alteration of the copy number and deletion of mitochondrial DNA in human hepatocellular carcinoma. Br J Cancer, 90, 2390-6.
- Yu M (2011). Generation, function and diagnostic value of mitochondrial DNA copy number alterations in human cancers. Life Sci, 89, 65-71. https://doi.org/10.1016/j.lfs.2011.05.010
- Yu M, Zhou Y, Shi Y, et al (2007). Reduced mitochondrial DNA copy number is correlated with tumor progression and prognosis in Chinese breast cancer patients. IUBMB Life, 59, 450-7. https://doi.org/10.1080/15216540701509955
- Zhu W, Qin W, Sauter ER (2004). Large-scale mitochondrial DNA deletion mutations and nuclear genome instability in human breast cancer. Cancer Detect Prev, 28, 119-26. https://doi.org/10.1016/j.cdp.2003.11.008
- Telomere length is correlated with mitochondrial DNA copy number in intestinal, but not diffuse, gastric cancer vol.14, pp.1, 2017, https://doi.org/10.3892/ol.2017.6197