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

Jung,Soo‑Jung; Cho,Ji‑Hyoung; Park,Won‑Jin; Heo,Yu‑Ran; Lee,Jae‑Ho

doi:10.3892/ol.2017.6197

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

Authors:
- Soo‑Jung Jung
- Ji‑Hyoung Cho
- Won‑Jin Park
- Yu‑Ran Heo
- Jae‑Ho Lee
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Affiliations: Department of Anatomy, School of Medicine, Keimyung University, Daegu, Republic of Korea, Department of General Surgery, School of Medicine, Keimyung University, Daegu, Republic of Korea
Published online on: May 17, 2017 https://doi.org/10.3892/ol.2017.6197
Pages: 925-929

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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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1	Jung KW, Won YJ, Oh CM, Kong HJ, Cho H, Lee JK, Lee DH and Lee KH: Prediction of cancer incidence and mortality in Korea, 2016. Cancer Res Treat. 48:451–457. 2016. View Article : Google Scholar : PubMed/NCBI
2	Correa P and Shiao YH: Phenotypic and genotypic events in gastric carcinogenesis. Cancer Res. 54 7 Suppl:1941s–1943s. 1994.PubMed/NCBI
3	Grabsch HI and Tan P: Gastric cancer pathology and underlying molecular mechanisms. Dig Surg. 30:150–158. 2013. View Article : Google Scholar : PubMed/NCBI
4	Yakirevich E and Resnick MB: Pathology of gastric cancer and its precursor lesions. Gastroenterol Clin North Am. 42:261–284. 2013. View Article : Google Scholar : PubMed/NCBI
5	Akhavan-Niaki H and Samadani AA: Molecular insight in gastric cancer induction: An overview of cancer stemness genes. Cell Biochem Biophy. 68:463–473. 2014. View Article : Google Scholar
6	Carcas LP: Gastric cancer review. J Carcinog. 13:142014. View Article : Google Scholar : PubMed/NCBI
7	Harley CB, Futcher AB and Greider CW: Telomeres shorten during ageing of human fibroblasts. Nature. 345:458–460. 1990. View Article : Google Scholar : PubMed/NCBI
8	Anderson S, Bankier AT, Barrell BG, De Bruijn MH, Coulson AR, Drouin J, Eperon IC, Nierlich DP, Roe BA, Sanger F, et al: Sequence and organization of the human mitochondrial genome. Nature. 290:457–465. 1981. View Article : Google Scholar : PubMed/NCBI
9	Blackburn EH, Greider CW and Szostak JW: Telomeres and telomerase: The path from maize, Tetrahymena and yeast to human cancer and aging. Nat Med. 12:1133–1138. 2006. View Article : Google Scholar : PubMed/NCBI
10	Blasco MA: Telomeres and human disease: Ageing, cancer and beyond. Nat Rev Genet. 6:611–622. 2005. View Article : Google Scholar : PubMed/NCBI
11	Cui H, Huang P, Wang Z, Zhang Y, Zhang Z, Xu W, Wang X, Han Y and Guo X: Association of decreased mitochondrial DNA content with the progression of colorectal cancer. BMC Cancer. 13:1102013. View Article : Google Scholar : PubMed/NCBI
12	Lee HC, Li SH, Lin JC, Wu CC, Yeh DC and Wei YH: Somatic mutations in the D-loop and decrease in the copy number of mitochondrial DNA in human hepatocellular carcinoma. Mut Res. 547:71–78. 2004. View Article : Google Scholar
13	Liao LM, Baccarelli A, Shu XO, Gao YT, Ji BT, Yang G, Li HL, Hoxha M, Dioni L, Rothman N, et al: Mitochondrial DNA copy number and risk of gastric cancer: A report from the Shanghai Women's Health Study. Cancer Epidemiol Biomarkers Prev. 20:1944–1949. 2011. View Article : Google Scholar : PubMed/NCBI
14	Wu X, Amos CI, Zhu Y, Zhao H, Grossman BH, Shay JW, Luo S, Hong WK and Spitz MR: Telomere dysfunction: A potential cancer predisposition factor. J Natl Cancer Inst. 95:1211–1218. 2003. View Article : Google Scholar : PubMed/NCBI
15	Kim JH, Kim HK, Ko JH, Bang H and Lee DC: The relationship between leukocyte mitochondrial DNA copy number and telomere length in community-dwelling elderly women. PloS one. 8:e672272013. View Article : Google Scholar : PubMed/NCBI
16	Qiu C, Enquobahrie DA, Gelaye B, Hevner K and Williams MA: The association between leukocyte telomere length and mitochondrial DNA copy number in pregnant women: A pilot study. Clin Lab. 61:363–369. 2015. View Article : Google Scholar : PubMed/NCBI
17	Tyrka AR, Carpenter LL, Kao HT, Porton B, Philip NS, Ridout SJ, Ridout KK and Price LH: Association of telomere length and mitochondrial DNA copy number in a community sample of healthy adults. Exp Gerontol. 66:17–20. 2015. View Article : Google Scholar : PubMed/NCBI
18	Passos JF, Saretzki G and von Zglinicki T: DNA damage in telomeres and mitochondria during cellular senescence: Is there a connection? Nucleic Acids Res. 35:7505–7513. 2007. View Article : Google Scholar : PubMed/NCBI
19	Hu J, Hwang SS, Liesa M, Gan B, Sahin E, Jaskelioff M, Ding Z, Ying H, Boutin AT, Zhang H, et al: Antitelomerase therapy provokes ALT and mitochondrial adaptive mechanisms in cancer. Cell. 148:651–663. 2012. View Article : Google Scholar : PubMed/NCBI
20	Sahin E, Colla S, Liesa M, Moslehi J, Müller FL, Guo M, Cooper M, Kotton D, Fabian AJ, Walkey C, et al: Telomere dysfunction induces metabolic and mitochondrial compromise. Nature. 470:359–365. 2011. View Article : Google Scholar : PubMed/NCBI
21	Lee H, Lee JH, Kim DC, Hwang I, Kang YN, Gwon GJ, Choi IJ and Kim S: Is mitochondrial DNA copy number associated with clinical characteristics and prognosis in gastric cancer? Asian Pac J Cancer Prev. 16:87–90. 2015. View Article : Google Scholar : PubMed/NCBI
22	Lee H, Jin JD, La BM, Park WJ, Choi IJ and Lee JH: TERT promoter mutation, telomere length and TERT expression in gastric cancer. Int J Clin Exp Pathol. 9:1758–1763. 2016.
23	Gil ME and Coetzer TL: Real-time quantitative PCR of telomere length. Mol Biotechnol. 27:169–172. 2004. View Article : Google Scholar : PubMed/NCBI
24	Lee JH, Hwang I, Kang YN, Choi IJ and Kim DK: Genetic characteristics of mitochondrial DNA was associated with colorectal carcinogenesis and its prognosis. PloS One. 10:e01186122015. View Article : Google Scholar : PubMed/NCBI
25	Tyrka AR, Parade SH, Price LH, Kao HT, Porton B, Philip NS, Welch ES and Carpenter LL: Alterations of mitochondrial DNA copy number and telomere length with early adversity and psychopathology. Biol Psychiatry. 79:78–86. 2016. View Article : Google Scholar : PubMed/NCBI
26	Aslan R, Bektas A, Bedir A, Alacam H, Aslan MS, Nar R, Yildirim B, Goren I, Ecemis O, Ustaoglu M, et al: Helicobacter pylori eradication increases telomere length in gastric mucosa. Hepatogastroenterology. 60:601–604. 2013.PubMed/NCBI
27	Pascua I, Fernández-Marcelo T, Sánchez-Pernaute A, De Juan C, Head J, Torres-García AJ and Iniesta P: Prognostic value of telomere function in gastric cancers with and without microsatellite instability. Eur J Gastroenterol Hepatol. 27:162–169. 2015. View Article : Google Scholar : PubMed/NCBI
28	Tahara T, Shibata T, Kawamura T, Ishizuka T, Okubo M, Nagasaka M, Nakagawa Y, Arisawa T, Ohmiya N and Hirata I: Telomere length in non-neoplastic gastric mucosa and its relationship to H. pylori infection, degree of gastritis and NSAID use. Clin Exp Med. 16:65–71. 2016. View Article : Google Scholar : PubMed/NCBI
29	Tahara T, Shibata T, Okubo M, Kawamura T, Horiguchi N, Ishizuka T, Nakani N, Nagasaka M, Nakagawa Y and Ohmiya N: Demonstration of potential link between helicobacter pylori related promoter CpG island methylation and telomere shortening in human gastric mucosa. Oncotarget. 7:43989–43996. 2016.PubMed/NCBI
30	Jeong CW, Lee JH, Sohn SS, Ryu SW and Kim DK: Mitochondrial microsatellite instability in gastric cancer and gastric epithelial dysplasia as a precancerous lesion. Cancer Epidemiol. 34:323–327. 2010. View Article : Google Scholar : PubMed/NCBI