Quantitative Assessment of the Diagnostic Role of CDH13 Promoter Methylation in Lung Cancer

  • Zhong, Yun-Hua (Faculty of Life Science and Technology, Kunming University of Science and Technology, Chenggong Campus) ;
  • Peng, Hao (Thoracic Surgery, the First People's Hospital of Yunnan Province, Panlong Campus) ;
  • Cheng, Hong-Zhong (Thoracic Surgery, the First People's Hospital of Yunnan Province, Panlong Campus) ;
  • Wang, Ping (Thoracic Surgery, the First People's Hospital of Yunnan Province, Panlong Campus)
  • Published : 2015.03.04


In order to explore the association between cadherin 13 (CDH13) gene promoter methylation and lung carcinoma (LC) risk, we carried out a meta-analysis with searching of PubMed, Web of Science. Ultimately, 17 articles were identified and analysised by STATA 12.0 software. Overall, we found a significant relationship between CDH13 promoter methylation and LC risk (odds ratio=6.98, 95% confidence interval: 4.21-11.56, p<0.001). Subgroup analyses further revealed that LC risk was increased for individuals carrying the methylated CDH13 compared with those with unmethylated CDH13. Hence, our study identified a strong association between CDH13 gene promoter methylation and LC and highlighted a promising potential for CDH13 methylation in LC risk prediction.


Supported by : Specialized Research Fund


  1. Stewart B (2014). World cancer report 2014. World Health Organization.
  2. Brock MV, Hooker CM, Ota-Machida E, et al (2008). DNA methylation markers and early recurrence in stage I lung cancer. N Engl J Med, 358, 1118-28.
  3. DerSimonian R, Laird N (1986). Meta-analysis in clinical trials. Control Clin Trials, 7, 177-88.
  4. Dickersin K, Berlin JA (1992). Meta-analysis: state-of-thescience. Epidemiol Rev, 14, 154-76.
  5. Dong SM, Lee EJ, Jeon ES, et al (2005). Progressive methylation during the serrated neoplasia pathway of the colorectum. Mod Pathol, 18, 170-8.
  6. Esteller M, Sanchez-Cespedes M, Rosell R, et al (1999). Detection of aberrant promoter hypermethylation of tumor suppressor genes in serum DNA from non-small cell lung cancer patients. Cancer Res, 59, 67-70.
  7. Feng Q, Hawes SE, Stern JE, et al (2007). Promoter hypermethylation of tumor suppressor genes in urine from patients with cervical neoplasia. Cancer Epidemiol Biomarkers Prev, 16, 1178-84.
  8. Feng Q, Hawes SE, Stern JE, et al (2008). DNA methylation in tumor and matched normal tissues from non-small cell lung cancer patients. Cancer Epidemiol Biomarkers Prev, 17, 645-54.
  9. Hanabata T, Tsukuda K, Toyooka S, et al (2004). DNA methylation of multiple genes and clinicopathological relationship of non-small cell lung cancers. Oncol Rep, 12, 177-80.
  10. Hsu HS, Chen TP, Hung CH, et al (2007). Characterization of a multiple epigenetic marker panel for lung cancer detection and risk assessment in plasma. Cancer, 110, 2019-26.
  11. Jemal A, Bray F, Center MM, et al (2011). Global cancer statistics. CA Cancer J Clin, 61, 69-90.
  12. Jin M, Kawakami K, Fukui Y, et al (2009). Different histological types of non-small cell lung cancer have distinct folate and DNA methylation levels. Cancer Sci, 100, 2325-30.
  13. Kim DS, Kim MJ, Lee JY, et al (2007). Aberrant methylation of E-cadherin and H-cadherin genes in nonsmall cell lung cancer and its relation to clinicopathologic features. Cancer, 110, 2785-92.
  14. Kim H, Kwon YM, Kim JS, et al (2006). Elevated mRNA levels of DNA methyltransferase-1 as an independent prognostic factor in primary nonsmall cell lung cancer. Cancer, 107, 1042-9.
  15. Kim H, Kwon YM, Kim JS, et al (2004). Tumor-specific methylation in bronchial lavage for the early detection of non-small-cell lung cancer. J Clin Oncol, 22, 2363-70.
  16. Kontic M, Stojsic J, Jovanovic D, et al (2012). Aberrant promoter methylation of CDH13 and MGMT genes is associated with clinicopathologic characteristics of primary non-small-cell lung carcinoma. Clin Lung Cancer, 13, 297-303.
  17. Lee SW (1996). H-cadherin, a novel cadherin with growth inhibitory functions and diminished expression in human breast cancer. Nat Med, 2, 776-82.
  18. Li L, Choi JY, Lee KM, et al (2012). DNA methylation in peripheral blood: a potential biomarker for cancer molecular epidemiology. J Epidemiol, 22, 384-94.
  19. M. Egger GDS, M. Schneider, and C. Minder (1997). Bias in meta-analysis detected by a simple, graphical test. BMJ Open.
  20. Mantel N, Haenszel W (1959). Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst, 22, 719-48.
  21. Mikeska T, Bock C, Do H, et al (2012). DNA methylation biomarkers in cancer: progress towards clinical implementation. Expert Rev Mol Diagn, 12, 473-87.
  22. Riou P, Saffroy R, Chenailler C, et al (2006). Expression of T-cadherin in tumor cells influences invasive potential of human hepatocellular carcinoma. Faseb J, 20, 2291-301.
  23. Sato M, Mori Y, Sakurada A, et al (1998). The H-cadherin (CDH13 ) gene is inactivated in human lung cancer. Human Genetics, 103, 96-101.
  24. Suzuki M, Shigematsu H, Iizasa T, et al (2006). Exclusive mutation in epidermal growth factor receptor gene, HER-2, and KRAS, and synchronous methylation of nonsmall cell lung cancer. Cancer, 106, 2200-7.
  25. Takeuchi T, Ohtsuki Y (2001). Recent progress in T-cadherin (CDH13 , H-cadherin) research. Histol Histopathol, 16, 1287-93.
  26. Toyooka KO, Toyooka S, Virmani AK, et al (2001). Loss of expression and aberrant methylation of the CDH13 (H-cadherin) gene in breast and lung carcinomas. Cancer Res, 61, 4556-60.
  27. Toyooka S, Maruyama R, Toyooka KO, et al (2003). Smoke exposure, histologic type and geography-related differences in the methylation profiles of non-small cell lung cancer. Int J Cancer, 103, 153-60.
  28. Tsou JA, Galler JS, Siegmund KD, et al (2007). Identification of a panel of sensitive and specific DNA methylation markers for lung adenocarcinoma. Mol Cancer, 6, 70.
  29. Ulivi P, Zoli W, Calistri D, et al (2006). p16INK4A and CDH13 hypermethylation in tumor and serum of non-small cell lung cancer patients. J Cell Physiol, 206, 611-5.
  30. Yanagawa N, Tamura G, Oizumi H, et al (2007). Promoter hypermethylation of RASSF1A and RUNX3 genes as an independent prognostic prediction marker in surgically resected non-small cell lung cancers. Lung Cancer, 58, 131-8.
  31. Zhai X, Li SJ (2014). Methylation of RASSF1A and CDH13 genes in individualized chemotherapy for patients with nonsmall cell lung cancer. Asian Pac J Cancer Prev, 15, 4925-8.
  32. Zhang Y, Wang R, Song H, et al (2011). Methylation of multiple genes as a candidate biomarker in non-small cell lung cancer. Cancer Lett, 303, 21-8.
  33. Zhong Y, Delgado Y, Gomez J, et al (2001). Loss of H-cadherin protein expression in human non-small cell lung cancer is associated with tumorigenicity. Clin Cancer Res, 7, 1683-7.

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