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| Correlation analysis between mitochondrial DNA D-LOOP point mutation and long-term chronic hepatitis and hepatocellular carcinoma |
| LIU Yun1 LIU Daojie2 QIAO Luxin1 CHEN Dexi1▲ |
1.Beijing Youan Hospital, Capital Medical University, Beijing Institute of Hepatology, Beijing 100069, China;
2.Laboratory Medicine, Haidian Maternal ＆ Child Health Hospital of Beijing City, Beijing 100080, China |
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Abstract Objective To analyze the changes in bases of mitochondrial DNA D-LOOP in various tissues by collecting specimens of hepatitis B virus (HBV)-associated liver cancer patients, and to explore the correlation between HBV-associated liver cancer and mitochondrial DNA D-LOOP. Methods Forty-six patients with chronic hepatitis B-related hepatocellular carcinoma (HCC) who were admitted to Beijing Youan Hospital, Capital Medical University from October 2008 to December 2019 were enrolled in the study. Thirty-one cases of cancerous tissues and corresponding adjacent tissues and peripheral blood, and 7 cases of adjacent tissues and corresponding peripheral blood, 5 cases of cancerous tissues and corresponding peripheral blood, 11 cases of cancer tissues and corresponding adjacent tissues. At the same time, 11 liver tissues from donors of liver transplantation patients and corresponding peripheral blood were selected as controls. The mitochondrial DNA of the specimen was extracted, primers and PCR reactions were designed to obtain the mitochondrial D-LOOP region, and the PCR product was sequenced for one generation. Results The results of one-generation sequencing data showed that long-term chronic HBV hepatitis caused a large number of single-base mutations in mitochondrial DNA D-LOOP region of inflammatory liver tissue and liver cancer, and the difference between liver cancer tissues and liver tissues was statistically significant (P < 0.05). Conclusion Long-term chronic HBV hepatitis can cause a large number of mitochondrial DNA D-LOOP region mutations in hepatitis tissues. Hepatoma tissue is different from normal liver tissue mutation mode, which has implications for the early diagnosis of liver cancer.
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[1] Torre LA，Bray F，Siegel RL，et al. Global cancer statistics，2012 [J]. CA Cancer J Clin，2015，65（2）：87-108.
[2] Perz JF，Armstrong GL，Farrington，LA，et al. The contributions of hepatitis B virus and hepatitis C virus infections to cirrhosis and primary liver cancer worldwide [J]. J Hepatol，2006，45（4）：529-538.
[3] Yuan K，Lei Y，Chen HN，et al. HBV-induced ROS accumulation promotes hepatocarcinogenesis through Snail-mediated epigenetic silencing of SOCS3 [J]. Cell Death Differ，2016，23（4）：616-627.
[4] Zhao Y，Liu S，Zhou L，et al. Aberrant shuttling of long noncoding RNAs during the mitochondria-nuclear crosstalk in hepatocellular carcinoma cells [J]. Am J Cancer Res，2019，9（5）：999-1008.
[5] Qiao L，Nie Z，Li Q，et al. Mitochondrial DNA depletion，mitochondrial mutations and high TFAM expression in hepatocellular carcinoma [J]. Oncotarget，2017，8（48）：84 373-84 383.
[6] Hikita H，Kodama T，Tanaka S，et al. Activation of the Mitochondrial Apoptotic Pathway Produces Reactive Oxygen Species and Oxidative Damage in Hepatocytes That Contribute to Liver Tumorigenesis [J]. Cancer Prev Res （Phila），2015，8（8）：693-701.
[7] Attardi G，Schatz G. Biogenesis of mitochondria [J]. Annu Rev Cell Biol，1988，4：289-333.
[8] Anderson S，Bankier AT，Barrell BG，et al. Sequence and organization of the human mitochondrial genome [J]. Nature，1981，290（5806）：457-465.
[9] Nishikawa M，Nishiguchi S，Kioka K，et al. Interferon reduces somatic mutation of mitochondrial DNA in liver tissues from chronic viral hepatitis patients [J]. J Viral Hepat，2005，12（5）：494-498.
[10] Li X，Guo X，Li D，et al. Multi-regional sequencing reveals intratumor heterogeneity and positive selection of somatic mtDNA mutations in hepatocellular carcinoma and colorectal cancer [J]. Int J Cancer，2018，143（5）：1143-1152.
[11] Yu C，Wang X，Huang L，et al. Deciphering the Spectrum of Mitochondrial DNA Mutations in Hepatocellular Carcinoma Using High-Throughput Sequencing [J]. Gene Expr，2018，18（2）：125-134.
[12] Attardi G，Schatz G. Biogenesis of mitochondria [J]. Annu Rev Cell Biol，1988，4：289-333.
[13] Baechler SA，Factor VM，Dalla Rosa I，et al. The mitochondrial type IB topoisomerase drives mitochondrial translation and carcinogenesis [J]. Nat Commun，2019，10（1）：83.
[14] Li S，Wan P，Peng T，et al. Associations between sequence variations in the mitochondrial DNA D-loop region and outcome of hepatocellular carcinoma [J]. Oncol Lett，2016，11（6）：3723-3728.
[15] Yin C，Cao HY，Chen YB，et al. NGS-based profiling reveals a critical contributing role of somatic D-loop mtDNA mutations in HBV-related hepatocarcinogenesis [J]. Ann Oncol，2019，30（6）：953-962.
[16] Chen T，Xun Z，Lin J，et al. Association between mitochondrial DNA content and baseline serum levels of HBsAg in chronic hepatitis B infection [J]. J Med Virol，2017，89（11）：1958-1962.
[17] Li L，Hann HW，Wan S，et al. Cell-free circulating mitochondrial DNA content and risk of hepatocellular carcinoma in patients with chronic HBV infection [J]. Sci Rep，2016，6（1）：23 992.
[18] Campo DS，Nayak V，Srinivasamoorthy G，et al. Entropy of mitochondrial DNA circulating in blood is associated with hepatocellular carcinoma [J]. BMC Med Genomics，2019，12（4）：74.
[19] Guo ZS，Jin CL，Yao ZJ，et al. Analysis of the Mitochondrial 4977 Bp Deletion in Patients with Hepatocellular Carcinoma [J]. Balkan J Med Genet，2017，20（1）：81-86.
[20] Gao Y，Nie HJ，Yang D，et al. Changes of the mitochondrial DNA copy number and the antioxidant system in the PBMC of hepatocellular carcinoma [J]. Zhongguo Ying Yong Sheng Li Xue Za Zhi，2016，32（1）：1-5. |
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