|Predictive value of CHFR and MLH1 methylation in human gastric cancer|
|Li, Yazhuo1,2; Yang, Yunsheng2; Lu, Youyong3; Herman, James G.4; Brock, Malcolm V.4; Zhao, Po5; Guo, Mingzhou2|
|关键词||Gastric cancer CHFR MLH1 RASSF1A MGMT DNA methylation DNA damage repair genes Chemo-sensitive marker|
|WOS标题词||Science & Technology|
|类目[WOS]||Oncology ; Gastroenterology & Hepatology|
|研究领域[WOS]||Oncology ; Gastroenterology & Hepatology|
|关键词[WOS]||CPG ISLAND HYPERMETHYLATION ; DNA MISMATCH REPAIR ; HMLH1 GENE PROMOTER ; DRUG-RESISTANCE ; OVARIAN-CANCER ; MICROTUBULE INHIBITORS ; PROTEIN EXPRESSION ; CLINICAL-RESPONSE ; CHEMOTHERAPY ; TUMORS|
Gastric carcinoma (GC) has one of the highest mortality rates of cancer diseases and has a high incidence rate in China. Palliative chemotherapy is the main treatment for advanced gastric cancer. It is necessary to compare the effectiveness and toxicities of different regimens. This study explores the possibility of methylation of DNA damage repair genes serving as a prognostic and chemo-sensitive marker in human gastric cancer.
The methylation status of five DNA damage repair genes (CHFR, FANCF, MGMT, MLH1, and RASSF1A) was detected by nested methylation-specific PCR in 102 paraffin-embedded gastric cancer samples. Chi-square or Fisher′s exact tests were used to evaluate the association of methylation status and clinic-pathological factors. The Kaplan-Meier method and Cox proportional hazards models were employed to analyze the association of methylation status and chemo-sensitivity.
The results indicate that CHFR, MLH1, RASSF1A, MGMT, and FANCF were methylated in 34.3 % (35/102), 21.6 % (22/102), 12.7 % (13/102), 9.8 % (10/102), and 0 % (0/102) of samples, respectively. No association was found between methylation of CHFR, MLH1, RASSF1A, MGMT, or FANCF with gender, age, tumor size, tumor differentiation, lymph node metastasis, and TNM stage. In docetaxel-treated gastric cancer patients, resistance to docetaxel was found in CHFR unmethylated patients by Cox proportional hazards model (HR 0.243, 95 % CI, 0.069-0.859, p = 0.028), and overall survival is longer in the CHFR methylated group compared with the CHFR unmethylated group (log-rank, p = 0.036). In oxaliplatin-treated gastric cancer patients, resistance to oxaliplatin was found in MLH1 methylated patients (HR 2.988, 95 % CI, 1.064-8.394, p = 0.038), and overall survival was longer in the MLH1 unmethylated group compared with the MLH1 methylated group (log-rank, p = 0.046).
CHFR is frequently methylated in human gastric cancer, and CHFR methylation may serve as a docetaxel-sensitive marker. MLH1 methylation was related to oxaliplatin resistance in gastric cancer patients.
|项目编号||2012CB934002 ; 2010CB912802 ; SS2012AA020314 ; SS2012AA020821 ; SS2012AA020303 ; 2011YQ03013405 ; 81121004 ; 81071953 ; 81161120432|
|资助机构||National Basic Research Program of China (973 Program) ; National High-tech R& ; D Program of China (863 Program) ; National Key Scientific instrument Special Programme of China ; National Science Foundation of China|
|作者单位||1.Chinese Peoples Liberat Army Gen Hosp, Dept Pathol, Sanya 572000, Hainan, Peoples R China|
2.Chinese Peoples Liberat Army Gen Hosp, Dept Gastroenterol & Hepatol, Beijing 100853, Peoples R China
3.Peking Univ, Key Lab Carcinogenesis & Translat Res, Mol Oncol Lab, Minist Educ,Canc Hosp & Inst, Beijing 10000, Peoples R China
4.Johns Hopkins Univ, Ctr Oncol, Baltimore, MD 21231 USA
5.Chinese Peoples Liberat Army Gen Hosp, Dept Pathol, Beijing 100853, Peoples R China
|Li, Yazhuo,Yang, Yunsheng,Lu, Youyong,et al. Predictive value of CHFR and MLH1 methylation in human gastric cancer[J]. GASTRIC CANCER,2015,18(2):280-287.|
|APA||Li, Yazhuo.,Yang, Yunsheng.,Lu, Youyong.,Herman, James G..,Brock, Malcolm V..,...&Guo, Mingzhou.(2015).Predictive value of CHFR and MLH1 methylation in human gastric cancer.GASTRIC CANCER,18(2),280-287.|
|MLA||Li, Yazhuo,et al."Predictive value of CHFR and MLH1 methylation in human gastric cancer".GASTRIC CANCER 18.2(2015):280-287.|