Journal of Society of Preventive Korean Medicine (대한예방한의학회지)

Society of Preventive Korean Medicine (대한예방한의학회)
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Identification of Potential Prognostic Biomarkers in lung cancer patients based on Pattern Identification of Traditional Korean Medicine Running title: A biomarker based on the Korean pattern identification for lung cancer

  • Ji Hye Kim (Laboratory of Clinical Biology and Pharmacogenomics, Department of Preventive Medicine, College of Korean Medicine, Kyung Hee University) ;
  • Hyun Sub Cheong (Department of Genetic Epidemiology, SNP Genetics, Inc.) ;
  • Chunhoo Cheon (Department of Preventive Medicine, College of Korean Medicine, Kyung Hee University) ;
  • Sooyeon Kang (Laboratory of Clinical Biology and Pharmacogenomics, Department of Preventive Medicine, College of Korean Medicine, Kyung Hee University) ;
  • Hyun Koo Kim (Department of Thoracic and Cardiovascular Surgery, Korea University Guro Hospital, Korea University College of Medicine) ;
  • Hyoung Doo Shin (Department of Genetic Epidemiology, SNP Genetics, Inc.) ;
  • Seong-Gyu Ko (Laboratory of Clinical Biology and Pharmacogenomics, Department of Preventive Medicine, College of Korean Medicine, Kyung Hee University)
  • Received : 2023.07.21
  • Accepted : 2023.08.12
  • Published : 2023.08.31
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Abstract

Objective : We studied prognostic biomarkers discovery for lung cancer based on the pattern identification for the personalized Korean medicine. Methods : Using 30 tissue samples, we performed a whole exome sequencing to examine the genetic differences among three groups. Results : The exome sequencing identified among 23,490 SNPs germline variants, 12 variants showed significant frequency differences between Xu and Stasis groups (P<0.0005). As similar, 18 and 10 variants were identified in analysis for Xu vs. Gentleness group and Stasis vs. Gentleness group, respectively (P<0.001). Our exome sequencing also found 8,792 lung cancer specific variants and among the groups identified 6, 34, and 12 variants which showed significant allele frequency differences in the comparison groups; Xu vs. Stasis, Xu vs. Gentleness group, and Stasis vs. Gentleness group. As a result of PCA analysis, in germline data set, Xu group was divided from other groups. Analysis using somatic variants also showed similar result. And in gene ontology analysis using pattern identification variants, we found genes like as FUT3, MYCBPAP, and ST5 were related to tumorigenicity, and tumor metastasis in comparison between Xu and Stasis. Other significant SNPs for two were responsible for eye morphogenesis and olfactory receptor activity. Classification of somatic pattern identification variants showed close relationship in multicellular organism reproduction, anion-anion antiporter activity, and GTPase regulator activity. Conclusions : Taken together, our study identified 40 variants in 29 genes in association with germline difference of pattern identification groups and 52 variants in 47 genes in somatic cancer tissues.

Keywords

Acknowledgement

The authors thank the families, patients, and control volunteers who participated in this research. The author thanks Mr. MJP for English editing support.

References

  1. Warr A, Robert C, Hume D, Archibald A, Deeb N, Watson M: Exome Sequencing: Current and Future Perspectives. G3 (Bethesda) 2015, 5(8):1543-1550. https://doi.org/10.1534/g3.115.018564
  2. Worthey EA, Mayer AN, Syverson GD, Helbling D, Bonacci BB, Decker B, Serpe JM, Dasu T, Tschannen MR, Veith RL et al: Making a definitive diagnosis: successful clinical application of whole exome sequencing in a child with intractable inflammatory bowel disease. Genet Med 2011, 13(3):255-262. https://doi.org/10.1097/GIM.0b013e3182088158
  3. Wang X, Wang H, Cao M, Li Z, Chen X, Patenia C, Gore A, Abboud EB, Al-Rajhi AA, Lewis RA et al : Whole-exome sequencing identifies ALMS1, IQCB1, CNGA3, and MYO7A mutations in patients with Leber congenital amaurosis. Hum Mutat 2011, 32(12):1450-1459. https://doi.org/10.1002/humu.21587
  4. Sassi C, Guerreiro R, Gibbs R, Ding J, Lupton MK, Troakes C, Lunnon K, Al-Sarraj S, Brown KS, Medway C et al: Exome sequencing identifies 2 novel presenilin 1 mutations (p.L166V and p.S230R) in British early-onset Alzheimer's disease. Neurobiol Aging 2014, 35(10):2422 e2413-2426.
  5. Byun M, Abhyankar A, Lelarge V, Plancoulaine S, Palanduz A, Telhan L, Boisson B, Picard C, Dewell S, Zhao C et al: Whole-exome sequencing-based discovery of STIM1 deficiency in a child with fatal classic Kaposi sarcoma. J Exp Med 2010, 207(11):2307-2312. https://doi.org/10.1084/jem.20101597
  6. Yan XJ, Xu J, Gu ZH, Pan CM, Lu G, Shen Y, Shi JY, Zhu YM, Tang L, Zhang XW et al: Exome sequencing identifies somatic mutations of DNA methyltransferase gene DNMT3A in acute monocytic leukemia. Nat Genet 2011, 43(4):309-315. https://doi.org/10.1038/ng.788
  7. Greif PA, Dufour A, Konstandin NP, Ksienzyk B, Zellmeier E, Tizazu B, Sturm J, Benthaus T, Herold T, Yaghmaie M et al: GATA2 zinc finger 1 mutations associated with biallelic CEBPA mutations define a unique genetic entity of acute myeloid leukemia. Blood 2012, 120(2):395-403. https://doi.org/10.1182/blood-2012-01-403220
  8. Snape K, Ruark E, Tarpey P, Renwick A, Turnbull C, Seal S, Murray A, Hanks S, Douglas J, Stratton MR et al: Predisposition gene identification in common cancers by exome sequencing: insights from familial breast cancer. Breast Cancer Res Treat 2012, 134(1):429-433. https://doi.org/10.1007/s10549-012-2057-x
  9. Cai J, Li L, Ye L, Jiang X, Shen L, Gao Z, Fang W, Huang F, Su T, Zhou Y et al: Exome sequencing reveals mutant genes with low penetrance involved in MEN2A-associated tumorigenesis. Endocr Relat Cancer 2015, 22(1):23-33. https://doi.org/10.1530/ERC-14-0225
  10. Chakraborty R, Savani BN, Litzow M, Mohty M, Hashmi S: A perspective on complementary/alternative medicine use among survivors of hematopoietic stem cell transplant: Benefits and uncertainties. Cancer 2015, 121(14):2303-2313. https://doi.org/10.1002/cncr.29382
  11. Efferth T, Li PC, Konkimalla VS, Kaina B: From traditional Chinese medicine to rational cancer therapy. Trends Mol Med 2007, 13(8):353-361. https://doi.org/10.1016/j.molmed.2007.07.001
  12. Kim JH, Shin YC, Ko SG: Integrating traditional medicine into modern inflammatory diseases care: multitargeting by Rhus verniciflua Stokes. Mediators Inflamm 2014, 2014:154561.
  13. Kim K-S KS-H, Eo W-K, Cheon S-H, Eom S-K, Jo H-J: Clinical research methodology for Traditional Korean Medicine treatment of lung cancer: Evidence-based approach. Journal of Korean Medical Classics 2010, 23(4):39-62.
  14. Park B-k LJ-h, Cho C-k, Shin H-k, Eom S-k, Yoo H-s. : Systemic review of clinical studies about Oriental medical treatment of cancer in Korea. Korean Journal of Oriental Internal Medicine 2008, 29(4):1061-1074.
  15. Swarup AB, Barrett W, Jazieh AR: The use of complementary and alternative medicine by cancer patients undergoing radiation therapy. Am J Clin Oncol 2006, 29(5):468-473. https://doi.org/10.1097/01.coc.0000221326.64636.b2
  16. Hunt KJ, Coelho HF, Wider B, Perry R, Hung SK, Terry R, Ernst E: Complementary and alternative medicine use in England: results from a national survey. Int J Clin Pract 2010, 64(11):1496-1502. https://doi.org/10.1111/j.1742-1241.2010.02484.x
  17. Adler SR, Fosket JR: Disclosing complementary and alternative medicine use in the medical encounter: a qualitative study in women with breast cancer. J Fam Pract 1999, 48(6):453-458.
  18. Gansler T, Kaw C, Crammer C, Smith T: A population-based study of prevalence of complementary methods use by cancer survivors: a report from the American Cancer Society's studies of cancer survivors. Cancer 2008, 113(5):1048-1057. https://doi.org/10.1002/cncr.23659
  19. Chen LL, Lin JS, Lin JD, Chang CH, Kuo HW, Liang WM, Su YC: BCQ+: a body constitution questionnaire to assess Yang-Xu. Part II: Evaluation of reliability and validity. Forsch Komplementmed 2009, 16(1):20-27. https://doi.org/10.1159/000197770
  20. Lin JD, Chen LL, Lin JS, Chang CH, Huang YC, Su YC: BCQ-: a body constitution questionnaire to assess Yin-Xu. Part I: establishment of a provisional version through a Delphi process. Forsch Komplementmed 2012, 19(5):234-241. https://doi.org/10.1159/000343580
  21. Lin JS, Chen LL, Lin JD, Chang CH, Huang CH, Mayer PK, Su YC: BCQ-: A Body Constitution Questionnaire to assess Yin-Xu. Part II: evaluation of reliability and validity. Forsch Komplementmed 2012, 19(6):285-292. https://doi.org/10.1159/000346060
  22. Su YC, Chen LL, Lin JD, Lin JS, Huang YC, Lai JS: BCQ+: a body constitution questionnaire to assess Yang-Xu. Part I: establishment of a first final version through a Delphi process. Forsch Komplementmed 2008, 15(6):327-334. https://doi.org/10.1159/000175938
  23. Chen Z, Wang P: Clinical Distribution and Molecular Basis of Traditional Chinese Medicine ZHENG in Cancer. Evid Based Complement Alternat Med 2012, 2012:783923.
  24. Dai J, Fang J, Sun S, Chen Q, Cao H, Zheng N, Zhang Y, Lu A: ZHENG-Omics Application in ZHENG Classification and Treatment: Chinese Personalized Medicine. Evid Based Complement Alternat Med 2013, 2013:235969.
  25. Berle CA, Cobbin D, Smith N, Zaslawski C: A novel approach to evaluate Traditional Chinese Medicine treatment outcomes using pattern identification. J Altern Complement Med 2010, 16(4):357-367. https://doi.org/10.1089/acm.2009.0367
  26. Jiang M, Zhang C, Zheng G, Guo H, Li L, Yang J, Lu C, Jia W, Lu A: Traditional chinese medicine zheng in the era of evidence-based medicine: a literature analysis. Evid Based Complement Alternat Med 2012, 2012:409568.
  27. Shi X, Tian L, Zhu XD, Wang HM, Qin H: Effect of Chinese drugs combining with chemotherapy on quality of life in 146 children with solid tumor. Chin J Integr Med 2011, 17(1):31-34. https://doi.org/10.1007/s11655-011-0608-3
  28. Hong J, Xiangwei W, Yanping C, Qionghui L, Wen L: An analysis of the long-term therapeutic effect of the integrated therapy of traditional Chinese medicine and radiotherapy on abdominal malignant tumor. J Tradit Chin Med 2005, 25(2):125-128.