Abstract Background The prognosis of thymic epithelial tumors (TETs) currently relies on the commonly adopted WHO classification and Masaoka staging system, which cannot reflect the undefined biological behaviors limiting them as prognostic factors. Methods In this study, we first identified 40 genes and 179 genes, respectively that were epigenetically upregulated and silenced, corresponding to a total of 509 functionally methylated CpG sites between thymomas and thymic carcinomas by using the TCGA dataset. Results The methylation β‐values of cg20068620 in MAPK4 and cg18770944 in USP51 were significantly associated with recurrence‐free survival (RFS). In the independent validation cohort, only WHO classification and methylation β‐values of cg20068620 in MAPK4 were independent prognostic factors for RFS in Chinese patients with TETs. A linear weighted model including these two factors was used to calculate the recurrence risk score (RRS). Time‐dependent ROC curve analysis revealed that RRS was overwhelmingly superior to WHO classification for predicting 3‐, 5‐, and 10‐year RFS and Masaoka stage for 3‐ and 5‐year RFS. Conclusions These results suggested that the methylation site cg20068620 in MAPK4 can improve the accuracy of the WHO classification alone regarding the prognostic value of TETs recurrence.

The current prognosis of thymic epithelial tumors (TETs) is according to the World Health Organization (WHO) histologic classification and the Masaoka staging system. These methods of prognosis have certain limitations in clinical application and there is a need to seek new method for determining the prognosis of patients with TETs. To date, there have been no studies done on the use of DNA methylation biomarkers for prognosis of TETs. The present study was therefore carried out to identify DNA methylation biomarkers that can determine the overall survival in patients with TETs.

BACKGROUND The objective is to investigate whether thymidylate synthase gene TS 5'-UTR polymorphism of peripheral blood mononuclear cells are associated with clinical outcomes of patients with stage II-III rectal adenocarcinoma treated with adjuvant 5-fluorouracil (5-FU) chemotherapy in Chinese population. METHODS One hundred and seventeen pathologically diagnosed colorectal adenocarcinoma patients with stage II-III, who underwent curative resection and received 5-fluoropyrimidine-based adjuvant chemotherapy were enrolled to this study. The 5'-TSER polymorphisms determined from the peripheral blood mononuclear cells were measured by Direct Sequencing. Kaplan-Meier curves and log-rank tests were used for survival analysis. The independent prognostic factors influencing DFS and OS were estimated by Cox proportional hazards model. RESULTS The distribution of TS 5'-UTR polymorphisms ware 2.6% 2R/2R, 31.6% 2R/3R and 65.8% 3R/3R respectively, which was fitted with Hard-Weinberg equilibrium (χ2=0.345, P=0.558). Stage, N stage, number of mesenteric lymph node metastasis, KPS, and 5'-UTR polymorphisms (2R/2R/2R/3R vs. 3R/3R, P<0.001) were significantly associated with DFS. Meanwhile, gender (female vs. male, P=0.025) and adjuvant radiotherapy (yes vs. no, P=0.025) were significantly associated with OS. Multivariate Cox regression showed that KPS score (HR =0.947, P=0.007), TS 5'-UTR polymorphism (HR =0.455, P=0.004) were independent prognostic factors for DFS. Whereas, KPS score was the only independent prognostic factors for OS (HR =0.910, P=0.005). CONCLUSIONS TS 5'-UTR tandem repeat polymorphisms had potential utilization for personalized therapy in Chinese population.