早期發現早期治療是癌症研究的主要目標。而DNA甲基化的異常可在癌症早期發現使得DNA甲基化生物標誌深具潛力。人類癌症的DNA甲基化變異及特定甲基化的改變通常與臨床特徵具相關性。DNA甲基化的生物標誌為早期發現、診斷、預後、分層治療及治療後療效監測提供了很大的潛力。再者，如何評價所取得的生物標誌之信心品質在個人化醫療同時也是一個很重要的議題。在本論文中，我們透過與人類胚胎幹細胞相關基因的甲基化狀態提出了一個新的策略以區分膠質母細胞瘤(Glioblastoma)病人之亞型並粹取出預後生物標誌組。接著，我們透過卵巢癌(High-grade Serous Ovarian Cancer)及乳癌(Breast Cancre)設計了一個評估生物標誌品質之機制，所設計的生物標誌品質評估機制將可自由運用至各種測試評估階段。由本研究之各實驗及統計檢定驗證之結果，顯示了所開發之方法，具強韌性且可取得各種癌症可信之預後型生物標誌。最後，本論文從膠質母細胞瘤，卵巢癌及乳癌所萃取出之生物標誌，不論其基因組在臨床試驗中，及未來個人化醫療措施，均深具未來應用及開發之潛力。

Achieving early detection of the onset of cancer is a major goal of cancer research. The early presence of aberrant DNA methylation makes the use of DNA methylation biomarkers an attractive possibility for early detection. Altered DNA methylation is ubiquitous in human cancers and specific methylation changes are often correlated with clinical features. DNA methylation biomarkers provide a range of opportunities for early detection, diagnosis, prognosis, therapeutic stratification and post-therapeutic monitoring. How to evaluate the obtained biomarkers is an another important issue in personalized medicine. In the dissertation, we propose a novel strategy can be used to stratify glioblastoma multiform (GBM) patients through the epigenetic states of genes associated with human embryonic stem cell (hESC) identity and the refined prognostic marker panel was extracted. Then, an evaluated mechanism for measuring the confident quality of biomarkers was established through high-grade serous ovarian cancer (HGSOC) and breast cancer. One could utilize the developed package for evaluating the quality of biomarkers in any stage of development. The dissertation contributed to 1) a strategy was established for stratifying cancer patients; 2) the refined prognostic marker panels are strong connected with literature with the potential for considering into clinical assay for patients’ stratification and future personalized medicine interventions; 3) a statistical examining mechanism was established for the confident quality of biomarkers measuring.

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