دورية أكاديمية
p16 Hypermethylation and KRAS Mutation Are Independent Predictors of Cetuximab Plus FOLFIRI Chemotherapy in Patients with Metastatic Colorectal Cancer
| العنوان: | p16 Hypermethylation and KRAS Mutation Are Independent Predictors of Cetuximab Plus FOLFIRI Chemotherapy in Patients with Metastatic Colorectal Cancer |
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| المساهمون: | College of Medicine, Dept. of Surgery, Se Hyun Kim, Kyu Hyun Park, Sang Joon Shin, Kang Young Lee, Tae Il Kim, Nam Kyu Kim, Sun Young Rha, Jae Kyung Roh, Joong Bae Ahn, Kim, Nam Kyu, Roh, Jae Kyung, Rha, Sun Young, Kim, Tae Il, Park, Kyu Hyun, Shin, Sang Joon, Ahn, Joong Bae, Lee, Kang Young |
| بيانات النشر: | Official journal of Korean Cancer Association Korea |
| سنة النشر: | 2016 |
| مصطلحات موضوعية: | CIMP, Colorectal neoplasms, KRAS, Methylation, p16 |
| الوصف: | PURPOSE: Hypermethylation of the CpG island of p16(INK4a) occurs in a significant proportion of colorectal cancer (CRC). We aimed to investigate its predictive role in CRC patients treated with 5-fluorouracil, leucovorin, irinotecan (FOLFIRI), and cetuximab. MATERIALS AND METHODS: Pyrosequencing was used to identify KRAS mutation and hypermethylation of 6 CpG island loci (p16, p14, MINT1, MINT2, MINT31, and hMLH1) in DNA extracted from formalin-fixed paraffin-embedded specimens. Logistic regression and Cox regression were performed for analysis of the relation between methylation status of CpG island methylator phenotype (CIMP) markers including p16 and clinical outcome. RESULTS: Hypermethylation of the p16 gene was detected in 14 of 49 patients (28.6%) and showed significant association with KRAS mutation (Fisher exact, p=0.01) and CIMP positivity (Fisher exact, p=0.002). Patients with p16-unmethylated tumors had significantly longer time to progression (TTP; median, 9.0 months vs. 3.5 months; log-rank, p=0.001) and overall survival (median, 44.9 months vs. 16.4 months; log-rank, p=0.008) than those with p16-methylated tumors. Patients with both KRAS and p16 aberrancy (n=6) had markedly shortened TTP (median, 2.8 months) compared to those with either KRAS or p16 aberrancy (n=11; median, 8.6 months; p=0.021) or those with neither (n=32; median, 9.0 months; p < 0.0001). In multivariate analysis, KRAS mutation and p16 methylation showed independent association with shorter TTP (KRAS mutation: hazard ratio [HR], 3.21; p=0.017; p16 methylation: HR, 2.97; p=0.027). CONCLUSION: Hypermethylation of p16 was predictive of clinical outcome in metastatic CRC patients treated with cetuximab and FOLFIRI, irrespective of KRAS mutation. ; open |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | 208~215 |
| اللغة: | English Korean |
| تدمد: | 1598-2998 2005-9256 |
| العلاقة: | CANCER RESEARCH AND TREATMENT; J00453; 2001~; ~2001 Journal of the Korean Cancer Research Association (���븳�븫�븰�쉶吏�); OAK-2016-01480; https://ir.ymlib.yonsei.ac.kr/handle/22282913/146601Test; T201600971; CANCER RESEARCH AND TREATMENT, Vol.48(1) : 208-215, 2016 |
| DOI: | 10.4143/crt.2014.314 |
| الإتاحة: | https://doi.org/10.4143/crt.2014.314Test https://ir.ymlib.yonsei.ac.kr/handle/22282913/146601Test |
| حقوق: | CC BY-NC-ND 2.0 KR ; https://creativecommons.org/licenses/by-nc-nd/2.0/krTest/ |
| رقم الانضمام: | edsbas.5BF49810 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 15982998 20059256 |
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| DOI: | 10.4143/crt.2014.314 |