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    題名: HMGA2與let-7a-5p對於具有不同APC基因狀態之大腸直腸癌病患化療反應的影響
    Effect of HMGA2 and let-7a-5p in chemotherapy response of colorectal cancer patients with different APC status
    作者: 劉滄柏
    Liu, Tsang-Pai
    貢獻者: 癌症生物學與藥物研發博士學位學程
    關鍵詞: 大腸直腸癌;HMGA2基因;Let-7a-5p微型核糖核酸
    CRC;HMGA2 gene;Let-7a-5p
    日期: 2018
    上傳時間: 2018-12-28 11:53:21 (UTC+8)
    摘要: 大腸直腸癌 (colorectal cancer, CRC) 之醫治準則是根據淋巴結轉移的程度給予輔助性化療。Let-7a-5p為一種微型核糖核酸，HMGA2為其下游標的基因，let-7a可藉由抑制HMGA2基因表現進而抑制腫瘤的轉移 (migration)、侵犯 (invasion) 以及上皮間質的轉化 (epithelial-mesenchymal transition, EMT)。本研究主要目的在探討let-7a-5p在大腸直腸癌的臨床研究上扮演之角色。
    本研究共收集192位大腸直腸癌病患之腫瘤及血液檢體，利用即時定量聚合酶鏈鎖反應以及免疫組織染色之方法分析病患血清以及腫瘤組織中let-7a-5p 與 HMGA2基因及蛋白的表現量。並且利用Kaplan–Meier之統計方法分析患者存活率、腫瘤復發與基因表現的相關性。
    本研究結果顯示，在大腸直腸癌患者腫瘤組織中的let-7a-5p表現量與其腫瘤大小、癌症分期以及有無發生淋巴結轉移呈現負相關 (腫瘤大小: p=0.024; 癌症分期: p≤0.0001; 有無發生淋巴結轉移: p<0.0001)。而且let-7a-5p與 HMGA2之間的蛋白表現量亦呈現負相關 (p<0.0001)。而手術治療後，同時具有let-7a-5p表現量低與HMGA2表現量高之病患的整體存活率 (overall survival, OS) 與無病存活率 (disease-free survival, DFS) 也比其他組別低。而在病患的血清與腫瘤組織中的let-7a-5p表現量亦呈現正相關。因此，本研究結果推測血清中的let-7a-5p表現量應該可以做為評估大腸癌患者臨床預後之生物指標。
    依據上述結果推測大腸直腸癌患者之血清以及腫瘤組織中，若出現低表現量的let-7a-5p，可以用以預測淋巴結轉移與否以及其病程發展情形。總結本研究之結果將有助於研究者與臨床醫師更了解let-7a-5p與HMGA2的表現在大腸直腸癌病程演進中所扮演的角色，及未來用於化學治療評估的可能性。
    Colorectal cancer (CRC) guidelines recommend adjuvant chemotherapy according to the level of lymph node metastasis. Let-7a-5p is a microRNA, which inhibits migration, invasion, as well as the epithelial-mesenchymal transition (EMT) by targeting HMGA2. The aim of this study was to investigate the role of let-7a-5p in the clinical impact of CRC.
    In this study, one hundred and ninety-two CRC patients were enrolled. The expression of let-7a-5p and HMGA2 in serum and tumor tissues were analysed by real-time PCR and immunohistochemistry. Kaplan–Meier analysis was used to analyse primary outcomes, including the survival and tumor recurrence.

    The expression of let-7a-5p in tumor tissues was significantly negative correlated with the tumor size, stage and lymph node metastasis in CRC patients (p=0.024 for tumor size, p≤0.0001 for stage and p<0.0001 for lymph node metastasis). There was a negative correlation between the levels of let-7a-5p and the HMGA2 protein (p<0.0001). The overall survival (OS) and disease-free survival (DFS) rates of patients with let-7a-5p low/HMGA2 high were poorer than those with let-7a-5p high/HMGA2 high, let-7a-5p high/HMGA2 low and let-7a-5p low/HMGA2 low. In addition, the expression levels of let-7a-5p in serums were positively correlated with let-7a-5p in the tumor tissues of the CRC patients. The expression levels of let-7a-5p in serums also could be used as biomarker to predict clinical outcome.
    We suggest that down-regulation of let-7a-5p in serums and tumor tissues of CRC patients could be used to predict lymph node metastasis and the disease prognosis. These results could be implicated for chemotherapy suggestion.
    描述: 博士
    指導教授：鄭雅文
    資料類型: thesis
    顯示於類別:[癌症生物學與藥物研發博士學位學程] 博碩士論文

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