Academic Journal
Association of CHFR Promoter Methylation with Treatment Outcomes of Irinotecan-Based Chemotherapy in Metastatic Colorectal Cancer
| العنوان: | Association of CHFR Promoter Methylation with Treatment Outcomes of Irinotecan-Based Chemotherapy in Metastatic Colorectal Cancer |
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| المؤلفون: | Yongjun Cha, Sun Young Kim, Hyun Yang Yeo, Ji Yeon Baek, Moon Ki Choi, Kyung Hae Jung, Seung Myung Dong, Hee Jin Chang |
| المصدر: | Neoplasia: An International Journal for Oncology Research, Vol 21, Iss 1, Pp 146-155 (2019) |
| بيانات النشر: | Elsevier |
| سنة النشر: | 2019 |
| المجموعة: | Directory of Open Access Journals: DOAJ Articles |
| مصطلحات موضوعية: | Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282 |
| الوصف: | Aberrant promoter methylation plays a vital role in colorectal carcinogenesis. However, its role in treatment responses is unclear, especially for metastatic disease. Here, we investigated the association between promoter methylation and treatment outcomes of irinotecan-based chemotherapy in 102 patients with metastatic colorectal cancer. Promoter methylation was examined by methylation-specific polymerase chain reaction for three loci (CHFR, WRN, and SULF2) associated with chemotherapy response and five CpG island methylator phenotype (CIMP)–specific markers (CACNA1G, IGF2, NEUROG1, RUNX3, and SOCS1). Association between CHFR methylation and in vitro sensitivity to irinotecan was also evaluated. Promoter methylation of CHFR, WRN, and SULF2 was identified in 16 (15.7%), 24 (23.5%), and 33 (32.4%) patients, respectively. CIMP status was positive in 22 (21.6%) patients. CHFR methylation was associated with a significantly longer time to progression (TTP) (median: 8.77 vs. 4.43 months, P = .019), with trends favoring higher overall survival (OS) (median: 22.83 vs. 20.17 months, P = .300) and response rates (31.3% vs. 17.4%, P = .300). For patients with unmethylated CHFR, TTP (median: 5.60 vs. 3.53, P = .020) and OS (median: 20.57 vs. 9.23, P = .006) were significantly different according to CIMP status. Colorectal cancer cell lines with CHFR methylation demonstrated increased sensitivity to irinotecan. Both CHFR overexpression and combination with 5-aza-2′-deoxycytidine reversed irinotecan sensitivity in CHFR-methylated cell lines, whereas CHFR knockdown in unmethylated cells restored sensitivity to irinotecan. These data suggest that CHFR methylation may be associated with favorable treatment outcomes of irinotecan-based chemotherapy in patients with metastatic colorectal cancer. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 1476-5586 |
| Relation: | http://www.sciencedirect.com/science/article/pii/S147655861830530X; https://doaj.org/toc/1476-5586; https://doaj.org/article/546385eb2f204dfa846e37ca29cc3121 |
| DOI: | 10.1016/j.neo.2018.11.010 |
| الاتاحة: | https://doi.org/10.1016/j.neo.2018.11.010 https://doaj.org/article/546385eb2f204dfa846e37ca29cc3121 |
| رقم الانضمام: | edsbas.DB4BDF21 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 14765586 |
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| DOI: | 10.1016/j.neo.2018.11.010 |