國人罹患大腸直腸癌患者比例居高第二，致死率更達所有癌別的第三位。主要原因為大腸癌初期篩檢不易，而進階的大腸鏡檢查有許多缺點。SHISA3是細胞中常見的抑癌基因，在許多腫瘤生長、浸潤和轉移過程中扮演著重要的角色，而SHISA3基因在大腸癌中失活，主要來自其表觀遺傳基因的改變。在大腸癌患者的腫瘤檢體中可偵測到高度甲基化的現象，及血漿中游離DNA的SHISA3的定序及分析，與健康者比較有明顯之差異，且隨著腫瘤的惡化程度血液中游離DNA的量也會遞增，且SHISA3基因在各CpG位點甲基化程度亦有增加的趨勢。同時大腸直腸癌患者血液中的抑癌基因SHISA3 DNA並不因腫瘤惡化而減少，在大腸癌的第二期腫瘤時更顯著增高。因此分析血漿中SHISA3甲基化並結合傳統檢驗，能有效提升檢測率並降低腫瘤致死率。分析血液中游離的SHISA3基因甲基化程度，可作為大腸直腸癌篩檢工具和大腸直腸癌分級的判斷之依據。

Colorectal cancer (CRC) accounts for the second-highest rate among other types of cancer and the mortality rate is the third-highest among other types of cancer in Taiwan [1-2]. The reason could be that CRC is hard to screen out in early stages and the colonoscopy is limited by technical interferences which also cause discomfort to subjects. SHISA3 is a novel tumor suppressor gene. Previous studies have suggested that SHISA3 could regulate the tumor growth, invasion and migration and the inactivation of SHISA3 DNA could be traced back to epigenomic alteration in CRC. Another research has also suggested that hypermethylated SHISA3 DNA can be detected in CRC specimens. In this study, the results have shown that an increasing amount of circulating free DNA (cfDNA) in CRC patient’s plasma compared to a healthy subject. Moreover, the quantity of cfDNA and the methylation rate (%) of SHISA3 at each CpG site may increase with the stage of CRC. Our results have also suggested that tumor cells will not reduce SHISA3 DNA in patient’s blood samples. Furthermore, the methylation of SHISA3 DNA in plasma increased as the tumor develops to the second stage. In conclusion, this study suggests that the combination of traditional tests and the screening of hypermethylation of SHISA3 gene in plasma could improve the detection efficiency and reduce CRC mortality. Additionally, the test of hypermethylation of SHISA3 also could be one of standards of the CRC classification.