ABSTRACT

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.

摘要

准确诊断脑转移瘤 (BMs) 的起源对于制定有效的治疗方法以改善患者的预后至关重要。来源不明的 BM 约占 BM 患者的 2-14%。因此，本研究的目的是根据其 DNA 甲基化谱确定 BM 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排序 (RMO)，确定了其他七种原发性癌症中每一种的逆转 CpG 位点对。然后，使用逆转 CpG 位点对，将 GM 与 BM 和其他七种原发性癌症区分开来。所有 61 个 GM 样本都被正确识别为 GM。还为非转基因样品确定了癌症类型。对于其他七种原发性癌症，每种癌症类型中超过 93% 的样本被正确识别为相应的癌症类型，但乳腺癌除外，其准确度为 88%。对于 133 个 BM 样本，132 个 BM 样本被确定为非转基因，133 个 BM 样本中有 95% 被正确分类为相应的原始癌症类型。基于 RMO 的方法可以准确识别 BMs 的来源，这对于精准治疗很重要。133 个 BM 样本中有 95% 被正确分类为相应的原始癌症类型。基于 RMO 的方法可以准确识别 BMs 的来源，这对于精准治疗很重要。133 个 BM 样本中有 95% 被正确分类为相应的原始癌症类型。基于 RMO 的方法可以准确识别 BMs 的来源，这对于精准治疗很重要。