Department of Bioinformatics, Key Laboratory of Ministry of Education for Gastrointestinal Cancer, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, 350122, China.
Department of General Surgery, Fuzhou Second Hospital Affiliated to Xiamen University, Fuzhou, 350007, China.
Epigenetics. 2021 Aug;16(8):908-916. doi: 10.1080/15592294.2020.1827720. Epub 2020 Oct 22.
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.
准确诊断脑转移瘤（BMs）的起源对于制定有效的治疗方案以改善患者预后至关重要。BMs 的起源不明约占 BMs 患者的 2-14%。因此，本研究旨在根据 DNA 甲基化谱确定 BMs 的原始癌症类型。收集了胶质瘤（GM）、BM 和其他七种原发性癌症的 DNA 甲基化谱。与 GM 相比，基于 CpG 位点的样本内相对甲基化顺序（RMO），为其他七种原发性癌症中的每一种确定了反转 CpG 位点对。然后，使用反转 CpG 位点对，将 GMs 与 BMs 和其他七种原发性癌症区分开来。61 个 GM 样本全部正确识别为 GM。非 GM 样本也确定了癌症类型。对于其他七种原发性癌症，每种癌症类型的样本中，大于 93%的样本被正确识别为其相应的癌症类型，除了乳腺癌，其准确率为 88%。对于 133 个 BM 样本，132 个 BM 样本被识别为非 GM，其中 95%的 BM 样本被正确分类到其相应的原始癌症类型。基于 RMO 的方法可以准确识别 BMs 的起源，这对于精准治疗很重要。
