2018/6/12

Role of LINE-1 methylation status of adjacent normal colonic mucus in the survival of Chinese patients with colon cancer.: Journal of Clinical Oncology: Vol 33, No 15_suppl

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GASTROINTESTINAL (COLORECTAL) CANCER

Role of LINE-1 methylation status of adjacent normal colonic mucus in the survival of Chinese patients with colon cancer.

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Changhua Zhuo, Qingguo Li, Dawei Li, Peng Lian, Xinxiang Li, Yiwei Li... Show More

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Abstract

DOI: 10.1200/jco.2015.33.15_suppl.e14514 Journal of Clinical Oncology 33,

e14514 Background: As a global epigenetic change, LINE-1 hypomethylation in normal mucosa were reported to have a key role in forming a ‘field defect’ in colorectal carcinogenesis. We aimed to study its influence on the survival of Chinese colon cancer patients. Methods: Tissue samples of tumor or normal mucosa were utilized to detect certain genetic and epigenetic modifications. Prognostic variables for the patients’ survivals were determined and the influence of LINE1 methylation rate (LMR) level was further analyzed by survival studies. Results: Overall, 127 patients, 83 males and 44 females, completed a median follow-up of 65 (3-85) months. It was revealed 14 (11.02%) and 5 (3.94%) cases mutated in KRAS and BRAF gene, respectively. Sixteen (12.60%) were confirmed as MSI-H, and 76 (59.84%) were found to have a loss of heterozygosity (LOH) at 18q. There were 26 (20.47%) cases defined as hypermethylation at hMLH1 gene promoter. A mean of 64.42 (9.45-86.93) % of LMRs were determined by pyrosequencing and further sub-grouped into high or low level by X-tile program. Cox multivariate analysis confirmed that the LMR level (high vs. low, HR = 0.396, 95% CI: 0.1940.805, p = 0.011), MSI status (MSI-H vs. MSS or MSI-L, HR = 0.082, 95% CI: 0.011-0.629, p = 0.016), and distant metastases (M1 vs. M0, HR = 28.006, 95% CI: 11.380-68.920, p = 0.000) were the independent prognostic factors for colon cancer specific survival. Sub-layer analysis revealed that patient with lower LMR level had a significantly worse survival in the subgroups of M0, right-sized colon, size 5 cm, Stage I-III, MSI-L or MSS, serum CEA at normal level, age > 60 years, 18q LOH, BRAF gene wild-types, KRAS gene mutation, etc. (all with p