Methylation of RASSF1A and CDH13 Genes in Individualized Chemotherapy for Patients with Non-small Cell Lung Cancer

  • Zhai, Xu (Clinical Laboratory Diagnostics, Graduate School, Dalian Medical University) ;
  • Li, Shi-Jun (Clinical Lab, First Affiliated Hospital of Dalian Medical University)
  • Published : 2014.06.30


Background: This study aimed to evaluate the methylation of RASSF1A and CDH13 gene promoter regions as a marker for monitoring chemotherapeutic efficacy with personalized medicine for patients with NSCLC, in the hope of providing a new direction for NSCLC individualized chemotherapy. Materials and Methods: 42 NSCLC patients and 40 healthy controls were included. Patient blood samples were collected in the whole process of chemotherapy. Methylation of RASSF1A and CDH13 gene promoter regions was detected by the methylation specific polymerase chain reaction (MSP). Results: The rate of RASSF1A and CDH13 gene methylation in 42 cases of NSCLC patients was significantly higher than in 40 healthy controls (52.4% to 0.0%, 54.8% to 0.0%, p<0.05). After the chemotherapy, the hyper-methylation of RASSF1A and CDH13 genes in PR group and SD group decreased significantly (p<0.05), and was significantly different from that in PD group (p<0.05), but not as compared with healthy controls (P>0.05). With chemotherapy, RASSF1A and CDH13 promoter region methylation rate in 42 cases of patients showed a declining trend. Conclusions: The methylation level of RASSF1A and CDH13 gene promoter region can reflect drug sensitivity of tumors to individualized treatment.


  1. Yong QD, Jiang SL, Shui BZ, et al (2013). Effect of 5-aza-2'-deoxycytidine on cell proliferation of non small cell lung cancer cell line A549 cells and expression of the TFPI-2 gene. Asian Pac J Cancer Prev, 14, 4421-6.
  2. Song Z, Zhang Y (2013). Efficacy of chemotherapy plus gefitinib treatment in advanced non-small-cell lung cancer patients following acquired resistance to gefitinib. Mol Clin Oncol, 1, 875-8.
  3. Vo T TL, Ta BT, Doan MT, et al (2013). Methylation Profile of BRCA1, RASSF1A and ER in Vietnamese women with ovarian cancer. Asian Pac J Cancer Prev, 14, 7713-8.
  4. Xinbing S, Na K, Minghua Z, et al (2013). Cotargeting EGFR and autophagy signaling: a novel therapeutic strategy for non-small-cell lung cancer. Mol Clin Oncol, 2, 8-12.
  5. Zinn RL, Pruitt K, Eguchi S, et al (2007). hTERT is expressed in cancer cell lines despite promoter DNA methylation by preserbation of unmethylated DNA and active chromatin aroud the transcription start site. Cancer Res, 67, 194-201.
  6. Milica Kontic, Jelena Stojsic, Dragana Jovanovic, et al (2012). Aberrant promoter methylation of CDH13 and MGMT genes is associated with clinicopathological characteristics of primary non small cell lung carcinoma. Clin Lung Cancer, 13, 297-303.
  7. Blattler A, Farnham PJ (2013). Cross-talk between site-specific transcription factors and DNA methylation states. J Biol Chem, 288, 34287-94.
  8. Jung UL, Hae JS, Ji WS (2012). Promoter Methylation of CDKN2A, $RAR\beta$, and RASSF1A in Non-Small Cell Lung Carcinoma: Quantitative Evaluation Using Pyrosequencing. Tuberc Respir Dis, 73, 11-21.
  9. Linda EC, Thomas J, Prof MT, et al (2009). Molecular predictive and prognostic markers in non-small-cell lung cancer. Lanc Oncol, 10, 1001-10.
  10. Nunomiya K, Shibata Y, Abe S, et al (2014). Relationship between serum level of lymphatic vessel endothelial hyaluronan receptor-1 and prognosis in patients with lung cancer. J Cancer, 5, 242-7.
  11. Pitroda SP, Pashatan M, Logan HL, et al (2014). DNA repair pathway gene expression score correlates with repair proficiency and tumor sensitivity to chemotherapy. Sci Transl Med, 6, 229-42.
  12. Qiang L, Junfeng G, Kelong M, et al (2009). RASSF1A, APC, ESR1, ABCB1 and HOXC9, but p16 INK4A, DAPK1, PTEN and MT1G genes were frequently methylated in the stage I non-small cell lung cancer in China. J Cancer Res Clin Oncol, 135, 1675-84.
  13. Shicheng G, Lixing T, Weilin P, et al (2014). Quantitative assessment of the diagnostic role of APC promoter methylation in non-small cell lung cancer. Clin Epig, 1, 229-38.
  14. Shin HH, Sey EL, Yu TC, et al (2014). Histological subtype and smoking status, but not gender, are associated with epidermal growth factor receptor mutations in non-small cell lung cancer. Mol Clin Oncol, 2, 252-8.

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