Identification of the origin of brain metastases based on the relative methylation orderings of CpG sites
Hui Liu,
Jianming Chen,
Haifeng Chen,
Jie Xia,
Ouxi Wang,
Jiajing Xie,
Meifeng Li,
Zheng Guo,
Guoping Chen,
Haidan Yan
Affiliations
Hui Liu
Department of Bioinformatics, Key Laboratory of Ministry of Education for Gastrointestinal Cancer, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, 350122, China
Jianming Chen
Department of General Surgery, Fuzhou Second Hospital Affiliated to Xiamen University, Fuzhou, 350007, China
Haifeng Chen
Department of General Surgery, Fuzhou Second Hospital Affiliated to Xiamen University, Fuzhou, 350007, China
Jie Xia
Department of Bioinformatics, Key Laboratory of Ministry of Education for Gastrointestinal Cancer, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, 350122, China
Ouxi Wang
Department of Bioinformatics, Key Laboratory of Ministry of Education for Gastrointestinal Cancer, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, 350122, China
Jiajing Xie
Department of Bioinformatics, Key Laboratory of Ministry of Education for Gastrointestinal Cancer, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, 350122, China
Meifeng Li
Department of Bioinformatics, Key Laboratory of Ministry of Education for Gastrointestinal Cancer, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, 350122, China
Zheng Guo
Department of Bioinformatics, Key Laboratory of Ministry of Education for Gastrointestinal Cancer, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, 350122, China
Guoping Chen
Department of General Surgery, Fuzhou Second Hospital Affiliated to Xiamen University, Fuzhou, 350007, China
Haidan Yan
Department of Bioinformatics, Key Laboratory of Ministry of Education for Gastrointestinal Cancer, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, 350122, China
Accurate diagnosis of the origin of brain metastases (BMs) is crucial for tailoring an effective therapy to improve patients’ prognosis. BMs of unknown origin account for approximately 2–14% of patients with BMs. Hence, the aim of this study was to identify the original cancer type of BMs based on their DNA methylation profiles. The DNA methylation profiles of glioma (GM), BM, and seven other types of primary cancers were collected. In comparison with GM, the reversal CpG site pairs were identified for each of the seven other types of primary cancers based on the within-sample relative methylation orderings (RMOs) of the CpG sites. Then, using the reversal CpG site pairs, GMs were distinguished from BMs and the seven other types of primary cancers. All 61 of the GM samples were correctly identified as GM. The cancer type was also identified for the non-GM samples. For the seven other types of primary cancers, greater than 93% of samples of each cancer type were correctly identified as their corresponding cancer type, except for breast cancer, which had an 88% accuracy. For 133 BM samples, 132 BM samples were identified as non-GM, and 95% of the 133 BM samples were correctly classified into their corresponding original cancer types. The RMO-based method can accurately identify the origin of BMs, which is important for precision treatment.
