Differential DNA methylation analysis of SUMF2, ADAMTS5, and PXDN provides novel insights into colorectal cancer prognosis prediction in Taiwan.

BACKGROUND: Patients with colorectal cancer (CRC) undergo surgery, as well as perioperative chemoradiation or adjuvant chemotherapy primarily based on the tumor-node- metastasis (TNM) cancer staging system. However, treatment responses and prognostic outcomes of patients within the same stage vary markedly. The potential use of novel biomarkers can improve prognostication and shared decision making before implementation into certain therapies. AIM: To investigate whether SUMF2, ADAMTS5, and PXDN methylation status could be associated with CRC prognosis. METHODS: We conducted a Taiwanese cohort study involving 208 patients with CRC recruited from Tri-Service General Hospital and applied the candidate gene approach to identify three genes involved in oncogenesis pathways. A methylation-specific polymerase chain reaction (MS-PCR) and EpiTYPER DNA methylation analysis were employed to detect methylation status and to quantify the methylation level of candidate genes in tumor tissue and adjacent normal tissue from participants. We evaluated SUMF2, ADAMTS5, and PXDN methylation as predictors of prognosis, including recurrence-free survival (RFS), progression-free survival (PFS), and overall survival (OS), using a Cox regression model and Kaplan-Meier analysis. RESULTS: We revealed various outcomes related to methylation and prognosis. Significantly shorter PFS and OS were associated with the CpG_3+CpG_7 hypermethylation of SUMF2 from tumor tissue compared with CpG_3+CpG_7 hypomethylation [hazard ratio (HR) = 2.24, 95% confidence interval (CI) = 1.03-4.85 for PFS, HR = 2.56 and 95%CI = 1.08-6.04 for OS]. By contrast, a significantly longer RFS was associated with CpG_2 and CpG_13 hypermethylation of ADAMTS5 from normal tissue compared with CpG_2 and CpG_13 hypomethylation [HR (95%CI) = 0.15 (0.03-0.71) for CpG_2 and 0.20 (0.04-0.97) for CpG_13]. The relationship between the methylation status of PXDN and the prognosis of CRC did not reach statistical significance. CONCLUSION: Our study found that CpG_3+CpG_7 hypermethylation of SUMF2 from tumor tissue was associated with significantly shorter PFS and OS compared with CpG_3+CpG_7 hypomethylation. CpG_2 and CpG_13 hypermethylation of ADAMTS5 from normal tissue was associated with a significantly longer RFS compared with CpG_2 and CpG_13 hypomethylation. These methylation-related biomarkers which have implications for CRC prognosis prediction may aid physicians in clinical decision-making.

Association between atopic dermatitis and colorectal cancer risk: A nationwide cohort study.

The role of atopic dermatitis (AD) in the development of colorectal cancer (CRC) has been a matter of scientific debate with mixed results. We conducted a nationwide cohort study to assess the association between AD and risk of CRC. Drawing on Taiwan's National Health Insurance Research Database, 46,703 patients with AD (the AD cohort) and 186,812 sex, age, and index year-matched patients without AD (the non-AD cohort) were identified in the period between 2000 and 2008. Follow-up time was calculated from the date of entry in the cohort until the occurrence of a first CRC diagnosis, death, or the end of the observation period (December 31, 2013), whichever occurred first. Hazards ratios (HRs) and accompanying 95% confidence intervals (CIs) derived from the Fine-Gray competing risk model were used to estimate the association between AD and CRC risk. After multivariable adjustment, AD was associated with an increased risk of CRC (adjusted HR, 1.26; 95% CI, 1.14-1.40). Of note, a significant positive association between AD and CRC risk was evident in both men and women and in all age groups. In summary, this population-based cohort study revealed that AD was associated with an increased risk of CRC in an Asian population. It will be of interest for cohort studies with prediagnostic specimens to evaluate the potential relationship between AD and CRC using biomarkers for allergy status.