Asian Pacific Journal of Cancer Prevention

Asian Pacific Journal of Cancer Prevention (아시아태평양암예방학회)
권호 표지
DOI QR코드

DOI QR Code

Combined Effects Methylation of FHIT, RASSF1A and RARβ Genes on Non-Small Cell Lung Cancer in the Chinese Population

  • Li, Wen (Key Laboratory of Green Packaging and Application of Biological Nanotechnology of Hunan Province, Hunan University of Technology) ;
  • Deng, Jing (Key Laboratory of Green Packaging and Application of Biological Nanotechnology of Hunan Province, Hunan University of Technology) ;
  • Tang, Jian-Xin (Key Laboratory of Green Packaging and Application of Biological Nanotechnology of Hunan Province, Hunan University of Technology)
  • Published : 2014.07.15
Download PDF
⟨ Previous Next ⟩

Abstract

Epigenetic modifications of tumour suppressor genes are involved in all kinds of human cancer. Aberrant promoter methylation is also considered to play an essential role in development of lung cancer, but the pathogenesis remains unclear.We collected the data of 112 subjects, including 56 diagnosed patients with lung cancer and 56 controls without cancer. Methylation of the FHIT, RASSF1A and RAR-${\beta}$ genes in DNA from all samples and the corresponding gene methylation status were assessed using the methylation-specific polymerase chain reaction (PCR, MSP). The results showed that the total frequency of separate gene methylation was significantly higher in lung cancer compared with controls (33.9-85.7 vs 0 %) (p<0.01).Similar outcomes were obtained from the aberrant methylation of combinations of any two or three genes (p<0.01). There was a tendency that the frequency of combinations of any two or three genes was higher in stage I+II than that in stage III+IV with lung cancer. However, no significant difference was found across various clinical stages and clinic pathological gradings of lung cancer (p>0.05).These observations suggest that there is a significant association of promoter methylation of individual genes with lung cancer risk, and that aberrant methylation of combination of any two or three genes may be associated with clinical stage in lung cancer patients and involved in the initiation of lung cancer tumorigenesis. Methylation of FHIT, RASSF1A and $RAR{\beta}$ genes may be related to progression of lung oncogenesis.

Keywords

References

  1. Al-Temaimi RA, Jacob S, Al-Ali W, et al (2013). Reduced FHIT expression is associated with mismatch repair deficient and high CpG island methylator phenotype colorectal cancer. Histochem Cytochem, 61, 627-38. https://doi.org/10.1369/0022155413497367
  2. Bodoor K, Haddad Y, Alkhateeb A, et al (2014). DNA hypermethylation of cell cycle (p15 and p16) and apoptotic (p14, p53, DAPK and TMS1) genes in peripheral blood of leukemia patients. Asian Pac J Cancer Prev, 15, 75-84. https://doi.org/10.7314/APJCP.2014.15.1.75
  3. Botana-Rial M, De Chiara L, Valverde D, et al (2012). Prognostic value of aberrant hypermethylation in pleural effusion of lung adenocarcinoma. Cancer Biol Ther, 13, 1436-42 . https://doi.org/10.4161/cbt.22004
  4. Chen X, Li P, Yang Z, et al (2013). Expression of fragile histidine triad (FHIT) and WW-domain oxidoreductase gene (WWOX) in nasopharyngeal carcinoma. Asian Pac J Cancer Prev, 14, 165-71. https://doi.org/10.7314/APJCP.2013.14.1.165
  5. Deng YF, Zhang L, Zhang XQ, et al (2012). Methylation of FHIT gene promoter region in DNA from plasma of patients with myelodysplastic syndromes and demethylating effect of decitabine. Zhongguo Shi Yan Xue Ye Xue Za Zhi, 20, 1144-8.
  6. Dumitrescu RG (2012). Epigenetic markers of early tumor development. Methods Mol Biol, 863, 3-14. https://doi.org/10.1007/978-1-61779-612-8_1
  7. Fiolka R, Zubor P, Janusicova V, et al (2013). Promoter hypermethylation of the tumor-suppressor genes RASSF1A, GSTP1 and CDH1 in endometrial cancer. Oncol Rep, 30, 2878-86. https://doi.org/10.3892/or.2013.2752
  8. Fujiwara K, Fujimoto N, Tabata M, et al (2005). Identification of epigenetic aberrant promoter methylation in serum DNA is useful for early detection of lung cancer. Clin Cancer Res, 11, 1219-25.
  9. Grote HJ, Schmiemann V, Geddert H, et al (2006). Methylation of RAS association domain family protein 1A as a biomarker of lung cancer. Cancer, 108, 129-34. https://doi.org/10.1002/cncr.21717
  10. Hesson LB, Cooper WN, Latif F (2007). The role of RASSF1A methylation in cancer. Dis Markers, 23, 73-87. https://doi.org/10.1155/2007/291538
  11. Jemal A, Siegel R, Ward E, et al (2009). Cancer statistics, 2009. CA Cancer J Clin, 59, 225-49. https://doi.org/10.3322/caac.20006
  12. Jeong YJ, Jeong HY, Lee SM, et al (2013). Promoter methylation status of the FHIT gene and Fhit expression: association with HER2/neu status in breast cancer patients. Oncol Rep, 30, 2270-8. https://doi.org/10.3892/or.2013.2668
  13. Ki KD, Lee SK, Tong SY, et al (2008). Role of 5'-CpG island hypermethylation of the FHIT gene in cervical carcinoma. J Gynecol Oncol, 19, 117-22. https://doi.org/10.3802/jgo.2008.19.2.117
  14. Ko E, Lee BB, Kim Y, Lee EJ, et al (2013). Association of RASSF1A and p63 with poor recurrence-free survival in node-negative stage I-II non-small cell lung cancer. Clin Cancer Res, 19, 1204-12. https://doi.org/10.1158/1078-0432.CCR-12-2848
  15. Li W, Deng J, Jiang P, et al (2012). Methylation of the RASSF1A and RAR$\beta$ genes as a candidate biomarker for lung cancer. Exp Ther Med, 3, 1067-71. https://doi.org/10.3892/etm.2012.517
  16. Liu WJ, Tan XH, Guo BP, et al (2013). Associations between RASSF1A promoter methylation and NSCLC: a meta-analysis of published data. Asian Pac J Cancer Prev, 14, 3719-24 https://doi.org/10.7314/APJCP.2013.14.6.3719
  17. Mengxi D, Qian W, Nan W, et al (2013). Effect of DNA methylation inhibitor on RASSF1A genes expression in non-small cell lung cancer cell line A549 and A549DDP. Cancer Cell Int, 13, 91. https://doi.org/10.1186/1475-2867-13-91
  18. Missaoui N, Hmissa S, Dante R, Frappart L, et al (2010). Global DNA methylation in precancerous and cancerous lesions of the uterine cervix. Asian Pac J Cancer Prev, 11, 1741-4.
  19. Moison C, Senamaud-Beaufort C, Fourriere L, et al (2013). DNA methylation associated with polycomb repression in retinoic acid receptor $\beta$ silencing. FASEB J, 27, 1468-78. https://doi.org/10.1096/fj.12-210971
  20. Neyaz MK, Kumar RS, Hussain S, et al (2008). Effect of aberrant promoter methylation of FHIT and RASSF1A genes on sudceptibility to cervical cancer in a North Indian population, Biomarkers, 13, 597-606. https://doi.org/10.1080/13547500802078859
  21. Toyooka S, Suzuki M, Maruyama R, et al (2004). The relationship between aberrant methylation and survival in non-small-cell lung cancers. Br J Cancer, 91, 771-4. https://doi.org/10.1038/sj.bjc.6602013
  22. Virmani AK, Rathi A, Zochbauer-Muller S, et al (2000). Gazdar AF Promoter methylation and silencing of the retinoic acid receptor-beta gene in lung carcinomas. J Natl Cancer Inst, 92, 1303-7. https://doi.org/10.1093/jnci/92.16.1303
  23. Vo LT, Thuan TB, Thu DM, et al (2013). Methylation profile of BRCA1, RASSF1A and ER in Vietnamese women with ovarian cancer. Asian Pac J Cancer Prev, 14, 7713-8. https://doi.org/10.7314/APJCP.2013.14.12.7713
  24. Zochbauer-Muller S, Minna JD, Gazdar AF (2002). Aberrant DNA methylation in lung cancer: biological and clinical implications. Oncologist, 7, 451-7. https://doi.org/10.1634/theoncologist.7-5-451
  25. Zuo H, Chan AS, Ammer H, et al (2013). Activation of G$\alpha$q subunits up-regulates the expression of the tumor suppressor Fhit. Cell Signal, 25, 2440-52. https://doi.org/10.1016/j.cellsig.2013.08.019

Cited by

  1. Association of RASSF1A Promoter Methylation with Lung Cancer Risk: a Meta-analysis vol.15, pp.23, 2014, https://doi.org/10.7314/APJCP.2014.15.23.10325
  2. Association of Methylation of the RAR-β Gene with Cigarette Smoking in Non-Small Cell Lung Cancer with Southern-central Chinese Population vol.15, pp.24, 2015, https://doi.org/10.7314/APJCP.2014.15.24.10937
  3. Aberrant Methylation of RASSF1A gene Contribute to the Risk of Renal Cell Carcinoma: a Meta-Analysis vol.16, pp.11, 2015, https://doi.org/10.7314/APJCP.2015.16.11.4665
  4. Analysis of FHIT Gene Methylation in Egyptian Breast Cancer Women: Association with Clinicopathological Features vol.16, pp.3, 2015, https://doi.org/10.7314/APJCP.2015.16.3.1235
  5. CUGBP1 promotes cell proliferation and suppresses apoptosis via down-regulating C/EBPα in human non-small cell lung cancers vol.32, pp.3, 2015, https://doi.org/10.1007/s12032-015-0544-8