Open AccessPromotor methylation status of MAPK4 is a novel epigenetic biomarker for prognosis of recurrence in patients with thymic epithelial tumors
Author(s) -
Guan Wei,
Li Songlin,
Zhang Zhimin,
Xiao He,
He Juan,
Li Jian,
He Xuan,
Luo Jia,
Liu Yun,
Lei Lin,
Ma Jungang,
Chen Lizhao,
Chen Chuan
Publication year - 2022
Publication title -
thoracic cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.823
H-Index - 28
eISSN - 1759-7714
pISSN - 1759-7706
DOI - 10.1111/1759-7714.14628
Subject(s) - medicine , methylation , cpg site , oncology , epigenetics , biomarker , cohort , proportional hazards model , stage (stratigraphy) , survival analysis , limiting , dna methylation , gene , gene expression , biology , genetics , engineering , mechanical engineering , paleontology
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.