title: DNA methylation of hMLH1 correlates with the clinical response to cisplatin after a surgical resection in Non-small cell lung cancer.
abstract: Our previous study demonstrated that promoter methylation of human mutL homolog 1 (hMLH1) is involved in determining sensitivity to cisplatin in NSCLC A549/DDP cell line, The present study was designed to determine whether DNA methylation of hMLH1 affects the prognosis of non-small cell lung cancer patients who received cisplatin-based adjuvant chemotherapy. Methylation status of hMLH1 was examined by nested methylation-specific PCR (nested MSP) in 84 archived NSCLC surgically resected tissue specimens from patients receiving cisplatin-based adjuvant chemotherapy. Univariate and multivariate analysis were used to investigate the relationship between hMLH1 methylation status and the clinical prognosis of the patients mentioned above. In the cohort of 84 NSCLC cases, 80 tissue samples were successfully amplified by nested MSP. Among them, 36 samples (45%) were identified to be methylated. Moreover, hMLH1 methylation was not associated with age, gender, smoking status, T stage, histology and differentiation, but correlated with lymphatic metastasis (P=0.021). Multivariate logistic regression analysis showed that hMLH1 methylation may function as a significant independent prognostic factor for tumor recurrence in NSCLC patients treated with adjuvant cisplatin (HR 3.114, 95% CI 1.032-9.399; P=0.044). However, Kaplan-Meier method (P=0.093) and multivariate Cox regression analysis (P=0.598) revealed that hMLH1 methylation was not associated with the survival of these patients. To conclude, the cisplatin-based adjuvant chemotherapy is more beneficial for NSCLC patients without hMLH1 methylation. hMLH1 methylation may have a potential to become a biomarker of individualized therapy for NSCLC patients.
authors.affiliation: Department of Oncology, The Second Xiangya Hospital of Central South University 139 Middle Renmin Road, Changsha 410011, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Wu
authors.affiliation: Department of Oncology, The Second Xiangya Hospital of Central South University 139 Middle Renmin Road, Changsha 410011, China.
authors.forename: Min
authors.initials: M
authors.lastname: Lu
authors.affiliation: Department of Oncology, The Second Xiangya Hospital of Central South University 139 Middle Renmin Road, Changsha 410011, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Qu
authors.affiliation: Department of Pathology, The Second Xiangya Hospital of Central South University 139 Middle Renmin Road, Changsha 410011, China.
authors.forename: Dai-Qiang
authors.initials: DQ
authors.lastname: Li
authors.affiliation: Department of Oncology, The Second Xiangya Hospital of Central South University 139 Middle Renmin Road, Changsha 410011, China.
authors.forename: Chun-Hong
authors.initials: CH
authors.lastname: Hu
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D002945:Cisplatin / Q000627:therapeutic use*; D019175:DNA Methylation; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D008297:Male; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D009687:Nuclear Proteins / Q000235:genetics*; D010597:Pharmacogenetics; D011401:Promoter Regions, Genetic; D016896:Treatment Outcome
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000970:Antineoplastic Agents; C501486:MLH1 protein, human; D009687:Nuclear Proteins; D000070957:MutL Protein Homolog 1; D002945:Cisplatin
keywords: NSCLC; cisplatin; hMLH1; hypermethylation; prognosis