Mitochondrial A10398G Alteration in Plasma Exosome of Non-small Cell Lung Cancer Patients
Authors: Quynh Nguyen Thuy , Thi Thanh Nhan Le , Lan Phuong Le , Phuong Thao Bui , Thi Tu Linh Nguyen , Trung Tho Le , Hong Thai Trinh 
Published: December 2020

This study identifies A10398G alteration of mitochondrial ND3 gene in plasma exosome of 29 non-small cell lung cancer (NSCLC) patients, 31 controls and 13 pairs of tumor tissue and adjacent tissue of NSCLC patients, thereby assessing the relationship between this alteration in plasma exosome and tissue as well as the pathological characteristics of NSCLC patients. Using the PCR-RFLP method, the homoplasmy and heteroplasmy of A10398G were initially identified in mitochondrial DNA from both exosomes and lung tissues. The rate of variant 10398G in plasma exosome was 62.1% in the NSCLC group and 61.3% in the control group. However, there was no statistically significant difference in A10398G between the patient and control groups. The alteration of A10398G in plasma exosome and in tissue correlated with each other (correlation coefficient 0.69; p = 0.009). However, this alteration was not related to age, gender, smoking, alcohol drinks status, tumor size, histological stage and TNM stage.

Keywords

A10398G alteration, mitochondrial DNA, plasma exosome, non-small cell lung cancer.

References

[1] Y. Zhang, Y. Liu, H. Liu, W.H. Tang, Exosomes: biogenesis, biologic function and clinical potential, Cell Biosci, 9 (2019) 19. https://doi.org/10.1186/s13578-019-0282-2.[2] H. Valadi, K. Ekström, A. Bossios, M. Sjöstrand, J.J. Lee, J.O. Lötvall, Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells, Nat Cell Biol, 9(6) (2007) 654–659. https://doi.org/10.1038/ncb1596.[3] A. Sharma & A. Johnson, Exosome DNA: Critical regulator of tumor immunity and a diagnostic biomarker, J Cell Physiol, 235(3) (2020) 1921–1932. https://doi.org/10.1002/jcp.29153.[4] Global Cancer Observatory, Cancer Today. https://gco.iarc.fr/today/online-analysis-pie. (accessed 05 November 2020).[5] A.A.M. Yusoff, F.N. Zulfakhar, S.Z.N.M. Khair, W.S.W. Abdullah, J.M. Abdullah, Z. Idris, Mitochondrial 10398A>G NADH-Dehydrogenase subunit 3 of complex I is frequently altered in intra-axial brain tumors in Malaysia, Brain Tumor Res Treat 6(1) (2018) 31–38. https://doi.org/10.14791/btrt.2018.6.e5.[6] P.T. Bich, N.N. Tu, N.T. Khuyen, Đ.M. Ha, T.V. To, T.H. Thai, The A10398G Alteration of Mitochondrial ND3 gene in Colorectal Cancer Patients, VNU Journal of Science: Medical and Pharmaceutical Sciences 34(2) (2018) 68. https://doi.org/10.25073/25881132/vnumps.4125. (in Vietnamese).[7] N.T.T. Linh, N.B. Hieu, Đ.M. Ha, T.V. To, T.H. Thai, Mitochondrial DNA A10398G Alteration in Breast Cancer Patients in Vietnam, VNU Journal of Science: Natural Sciences and Technology 31(2) (2015) 36. (in Vietnamese).[8] R.K. Bai, S.M. Leal, D. Covarrubias, A. Liu and L.J.C. Wong, Mitochondrial genetic background modifies breast cancer risk, Cancer Res 67(10) (2017) 4687-4694. https://doi.org/10.1158/0008-5472.CAN-06-3554.[9] J.A. Canter, A.R. Kallianpur, F.F. Parl, R.C. Millikan, Mitochondrial DNA G10398A polymorphism and invasive breast cancer in African-American women, Cancer Res 65(17) (2005) 8028-8033. https://doi.org/10.1158/0008-5472.can-05-1428.[10] K. Darvishi, S. Sharma, A.K. Bhat, E. Rai, R.N.K. Bamezai, Mitochondrial DNA G10398A polymorphism imparts maternal Haplogroup N a risk for breast and esophageal cancer, Cancer Letts 249(2) (2017) 249-255. https://doi.org/10.1016/j.canlet.2006.09.005.[11] S.H.H. Juo, M.Y. Lu, R.K. Bai, Y.C. Liao, R.B. Trieu, M.L. Yu, L.J.C Wong, A common mitochondrial polymorphism 10398A>G is associated metabolic syndrome in a Chinese population, Mitochondrion 10(3) (2010) 294-299. https://doi.org/10.1016/j.mito.2010.01.001.[12] H. Xu, W. He, H.G. Jiang, H. Zhao, X.H. Peng, Y.H. Wei, J.N. Wei, C.H. Xie, C. Liang, Y.H. Zhong, G. Zhang, D. Deng, Y.F. Zhou, F.X. Zhou, Prognostic value of mitochondrial DNA content and G10398A polymorphism in non-small cell lung cancer, Oncol Rep 30(6) (2013) 3006-3012. https://doi.org/10.3892/or.2013.2783.[13] Y. Qi, Y. Wei, Q. Wang, H. Xu, Y. Wang, A. Yao, H. Yang, Y. Gao, F. Zhou, Heteroplasmy of mutant mitochondrial DNA A10398G and analysis of its prognostic value in non-small cell lung cancer, Oncol Lett 12(5) (2016) 3081-3088. https://doi.org/10.3892/ol.2016.5086.[14] A.M. Czarnecka, T. Krawczyk, M. Zdrozny, J. Lubiński, R.S. Arnold, W. Kukwa, A. Scińska, P. Golik, E. Bartnik, J.A. Petros, Mitochondrial NADH-dehydrogenase subunit 3 (ND3) polymorphism (A10398G) and sporadic breast cancer in Poland, Breast Cancer Res Treat 121(2) (2010) 511-518. https://doi.org/10.1007/s10549-009-0358-5.[15] M. Guescini, S. Genedani, V. Stocchi & L. F.Agnati, Astrocytes and Glioblastoma cells release exosomes carrying mtDNA, J Neural Transm (Vienna), 117(1) (2010) 1–4. https://doi.org/10.1007/s00702-009-0288-8.[16] P. Sansone, C. Savini, I. Kurelac, Q. Chang, L.B. Amato, A. Strillacci, A. Stepanova, L. Iommarini, C. Mastroleo, L. Daly, A. Galkin, B.K. Thakur, N. Soplop, K. Uryu, A. Hoshino, L. Norton, M. Bonafé, M. Cricca, G. Gasparre, D. Lyden, and J. Bromberg, Packaging and transfer of mitochondrial DNA via exosomes regulate escape from dormancy in hormonal therapy-resistant breast cancer, PNAS, 114(43) (2017) E9066-9075. https://doi.org/10.1073/pnas.1704862114.