Adverse prognostic impact of the CpG island methylator phenotype in metastatic colorectal cancer

作者：Cha Yongjun; Kim Kyung Ju; Han Sae Won^*; Rhee Ye Young; Bae Jeong Mo; Wen Xianyu; Cho Nam Yun; Lee Dae Won; Lee Kyung Hun; Kim Tae Yong; Oh Do Youn; Im Seock Ah; Bang Yung Jue; Jeong Seung Yong; Park Kyu Joo; Kang Gyeong Hoon^*; Kim Tae You

来源：British Journal of Cancer, 2016, 115(2): 164-171.

DOI：10.1038/bjc.2016.176

• colorectal cancer
• CpG island methylator phenotype
• chemotherapy
• prognosis

Background: The association between the CpG island methylator phenotype (CIMP) and clinical outcomes in metastatic colorectal cancer remains unclear. We investigated the prognostic impact of CIMP in patients with metastatic colorectal cancer treated with systemic chemotherapy.
Methods: Eight CIMP-specific promoters (CACNA1G, IGF2, NEUROG1, RUNX3, SOCS1, CDKN2A, CRABP1, and MLH1) were examined. The CIMP status was determined by the number of methylated promoters as high (>= 5), low (1-4), and negative (0).
Results: A total of 153 patients were included (men/women, 103/50; median age, 61 years; range, 22-80 years). The CIMP status was negative/low/high in 77/69/7 patients, respectively. Overall survival (OS) was significantly different among the three CIMP groups, with median values of 35.7, 22.2, and 9.77 months for the negative, low, and high groups, respectively (P<0.001). For patients treated with fluoropyrimidine and oxaliplatin first-line chemotherapy (N = 128), OS and progression-free survival (PFS) were significantly different among the three CIMP groups; the median OS was 37.9, 23.8, and 6.77 months for the negative, low, and high groups, respectively (P<0.001), while the median PFS was 9.97, 7.87, and 1.83 months, respectively (P = 0.002). Response rates were marginally different among the three CIMP groups (53.4% vs 45.1% vs 16.7%, respectively; P = 0.107). For patients treated with fluoropyrimidine and irinotecan second-line chemotherapy (N = 86), only OS showed a difference according to the CIMP status, with median values of 20.4, 13.4, and 2.90 months for the negative, low, and high groups, respectively (P<0.001).
Conclusions: The CIMP status is a negative prognostic factor for patients with metastatic colorectal cancer treated with chemotherapy.

• 出版日期2016-7-12