臺灣博碩士論文加值系統

研究目的：NOTCH基因的表現已被證明是一個重要的肺癌致癌基因。所以有必要去深入了解NOTCH基因的表現與肺癌產生之間的關係。本研究即在探討NOTCH基因的表現在非小細胞肺癌中表現量的差異及其對肺癌患者預後產生之影響。
研究方法：自2001年至2011年期間，被診斷為非小細胞肺癌，且同時接受手術切除之患者，為本研究納入之對象。NOTCH基因的表現量則表示以逆轉錄聚合酶鏈式反應(reverse transcription-polymerase chain reaction, RT-PCR)之結果。患者之臨床基本資料、病理組織學型態、癌症分期與病患之預後均納入分析。
研究結果：本研究共有97位非小細胞肺癌術後之患者接受NOTCH1 到 NOTCH4基因之檢測。其中58位病患(59.8%)為男性，平均年紀為67.0 ± 11.1歲。其中75位為肺腺癌之患者(77.3%)，19位病患為鱗狀細胞癌(19.6%)。肺腺癌相較於其他的組織型態有較高之NOTCH2的表現量(p值 < 0.001)。另一方面，鱗狀細胞癌相較於其他之組織型態有較高之NOTCH1及NOTCH3的表現量(p值 = 0.014及p 值 = 0.032)。肺癌患者若有較高之NOTCH2的表現，則肺癌復發的機會愈高。肺腺癌之患者中若有較高的NOTCH1或NOTCH3的表現量，則有較差之無疾病惡化存活期 (無疾病惡化存活期中位數，NOTCH1：7.2 v.s 21.2月， p值 = 0.03； NOTCH3：12.0 v.s. 25.3月，p值 = 0.05)。肺腺癌之患者若NOTCH1和NOTCH3同時均為高表現量者與其他或NOTCH1和NOTCH3同時均為低表現量者相比有較差的無疾病惡化存活期 (7.2 v.s. 14.2 v.s 25.3月，p值 = 0.03)。然而NOTCH基因表現量的高低則與肺癌患者之整體存活期無相關。
研究結論：肺腺癌的患者有較高之NOTCH2的表現量。肺癌患者若有較高之NOTCH2的表現，則肺癌復發的機會愈高。肺腺癌之患者中若同時有較高的NOTCH1與NOTCH3的表現量，則有較差之無疾病惡化存活期。

RATIONALE: Notch signaling has been demonstrated to frequently participate in the process of lung carcinogenesis. Thus it is important to understand the role of Notch expression in lung cancer development. This study aimed to search Notch expression in non-small cell lung cancer (NSCLC) and its impact on survival.

METHODS: From 2001 to 2011, patients with diagnosis of NSCLC who received surgical resection were included. The expression of Notch pathway elements was assessed by real-time polymerase chain reaction (RT-PCR). Clinical characteristics, histological types, disease stages, and outcomes were analyzed.

RESULTS: Ninety-seven patients with NSCLC being explored the expression of Notch gene (Notch 1 – 4, and Notch 2 N-terminal ligand). Fifty-eight patients (59.8%) were male. The mean age was 67.0 ± 11.1 years old. Seventy-five patients (77.3%) were adenocarcinoma, 19 patients (19.6%) were squamous cell carcinoma. Patients with adenocarcinoma had higher expression of Notch 2 and Notch 2 N-terminal ligand (NL) than other histology types (p < 0.001 and p = 0.001, respectively). Otherwise, patients with squamous cell carcinoma had relative higher expression of Notch 1 and Notch 3 expression than other histology types (p = 0.014 and p = 0.032, respectively). Patients who had cancer recurrence also had higher Notch 2 expression (p = 0.008). Patients with adenocarcinoma who had higher Notch 1 or Notch 3 expression had poor progression-free survival (PFS) (PFS, median, Notch1: 7.2 v.s 21.2 mpnths, p = 0.03; and Notch3: 12.0 v.s. 25.3 months, p = 0.05, respectively). There was also a shorter median PFS in the patient group with lung adenocarcinoma of both high expression of Notch1 and Notch3 than those with both high expression of Notch1 and Notch3 group (both high vs. others v.s both low: PFS, median, 7.2 v.s. 14.2 v.s 25.3 months，p = 0.03). However, the expression of Notch signaling had no impact on overall survival.

CONCLUSIONS: Patients with lung adenocarcinoma had higher Notch2 expression. Patients with higher Notch2 expression also had higher rate of cancer recurrence. Both higher Notch1 and Notch3 expression was associated with poor prognosis in lung adenocarcinoma.

口試委員會審定書 i
致謝 ii
中文摘要 iii
英文摘要 iv
論文內容
一、前言 1
二、研究方法 2
三、結果 4
四、討論 7
五、參考文獻 9
六、圖表 14
圖一、NOTCH基因在不同組織型態之表現 14
圖二、NOTCH基因在不同肺癌分期之表現 18
圖三、免疫組織化學染色法顯示肺線癌細胞內NOTCH2的表現量 20
圖四、NOTCH基因的表現量與肺腺癌預後的相關性 24
圖五、結合NOTCH1 與NOTCH3基因的表現量與肺腺癌預後的相關性 26
表一、97位接受手術切除之非小細胞肺癌患者接受NOTCH基因分析之臨床基本資料 27
表二、以COX回歸模式分析肺腺癌患者NOTCH基因之表現量對無疾病惡化存活期之影響 28
七、附錄 29
八、英文論文 33

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