Abstract
BackgroundLow methylation status of LINE-1 in tumors is associated with poor survival in patients with colon cancer. Eastern Cooperative Oncology Group performance status (ECOG-PS) is a method to assess the functional status of a patient. We retrospectively evaluated the relationship between ECOG-PS and LINE-1 methylation in colorectal cancers (CRCs) and their prognostic impact in CRC or colon cancer patients receiving adjuvant 5-fluorouracil/leucovorin/oxaliplatin (FOLFOX).ResultsLINE-1 methylation and microsatellite instability were analyzed in stage III or high-risk stage II CRCs (n = 336). LINE-1 methylation levels were correlated with clinicopathological features, including PS and recurrence-free survival (RFS). The association between the tumoral LINE-1 methylation level and PS was observed (OR = 2.56, P < 0.001). Differences in LINE-1 methylation levels in cancer tissue between the PS 0 and 1 groups were significant in patients older than 60 years (P = 0.001), the overweight body mass index group (P = 0.005), and the stage III disease group (P = 0.008). Prognostic significances of LINE-1 methylation status or combined PS and LINE-1 methylation statuses were identified in stage III colon cancers, not in stage III and high-risk stage II CRCs. Low LINE-1 methylation status was closely associated with a shorter RFS time. The difference between PS(0)/LINE-1(high) and PS(≥1)/LINE-1(low) was significant, which suggests that colon cancer patients with concurrent PS(≥1)/LINE-1 (low) have a higher recurrence rate.ConclusionsPS was associated with LINE-1 methylation in CRC tissue. LINE-1 methylation was associated with RFS in stage III colon cancer patients who were treated with adjuvant FOLFOX chemotherapy. Combined PS and LINE-1 methylation status might serve as a useful predictor of cancer recurrence.Electronic supplementary materialThe online version of this article (doi:10.1186/s13148-016-0203-8) contains supplementary material, which is available to authorized users.
Highlights
Low methylation status of Long interspersed nucleotide element-1 (LINE-1) in tumors is associated with poor survival in patients with colon cancer
Combined performance status (PS) and LINE-1 methylation status might serve as a useful predictor of cancer recurrence
The present study has demonstrated that Eastern Cooperative Oncology Group performance status (ECOG-PS) was associated with LINE-1 methylation in cancer tissue
Summary
Low methylation status of LINE-1 in tumors is associated with poor survival in patients with colon cancer. We retrospectively evaluated the relationship between ECOG-PS and LINE-1 methylation in colorectal cancers (CRCs) and their prognostic impact in CRC or colon cancer patients receiving adjuvant 5-fluorouracil/ leucovorin/oxaliplatin (FOLFOX). Hypomethylation of LINE-1 is a common finding in various tissue types of human cancer, and recent meta-analysis results have shown that LINE-1 methylation levels are significantly lower in cancer tissues than in paired normal tissues, and especially in CRC and gastric cancer [10,11,12,13,14,15,16,17]. In some tissue types of human cancer, including CRC, tumoral LINE-1 hypomethylation is associated with a poor clinical outcome [14, 15, 18,19,20,21]
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