FEN1 和 RAD54B 的 過度表達可能作為肺腺癌的獨立預後因素

The overexpression of FEN1 and RAD54B may act as independent prognostic factors of lung adenocarcinoma

黃昭群(Jau-Chung Hwang)

指導教授 ： 劉大智

高雄醫學大學/醫學院/臨床醫學研究所/碩士(2015年)

https://doi.org/10.6832/KMU.2015.00149

摘要

中文摘要 研究背景:癌症是人類重要的死亡因素之一。我國國人死因統計結果顯示，連續三十年的十大死因仍以癌症居首。肺癌又高居癌症死亡原因的首位，也是全球性的，與日俱增的癌。因此肺癌成為急須迫切研究的課題。最近一二十年來,對酵母菌和果蠅的研究發現,在某些情況下,當這些生物只有單一個基因發生突變時，細胞可存活；而當細胞同時發生兩個基因的突變時，細胞就無法繼續存活，具有這種關係的兩基因，稱之為合成致死(synthetic lethality,SL)。經由分析癌細胞合成致死相關基因的蛋白質表現,來了解肺癌細胞對這些基因的依賴性與病人的預後之間的關係,進一步發展可行的治療方法。
研究方法: 1998年至2010年，共有93例肺腺癌患者入選本研究並收集和整理病人臨床資料。在所有患者中肺癌組織微陣列組織點進行24個基因配對免疫組織化學（Immunohistochemical, IHC）染色。免疫組化染色結果由2位病理醫師判讀。經由統計方法分析肺癌病人的存活曲線和世代性的追蹤與基因表達相關的風險比（Hazard ratio,HR）。
結果: 24個基因配對中，只有FEN1（片段核酸內切酶1）和RAD54B（脱氧核糖核酸修復和重组蛋白RAD54同源物B）共同過度表達的肺腺癌患者預後較差。
患者FEN1和RAD54B皆表達者顯著較差的預後 (多變量分析：HR=2.35，95％CI=1.13-4.91，P =0.0230)。與只有單一的基因表達相比較，患者的兩個基因皆表達時，5年存活率也顯著降低。這些結果表明，FEN1和RAD54B的組合表達可能是肺腺癌患者預後不良的一個獨立的標誌物。
結論: 預後不佳的肺腺癌病患中FEN1和RAD54B的過度表達說明這兩個基因可能是潛在的標記物，可用於篩選高風險的患者，並可能發展出有效的個人化
療法。

關鍵字

肺腺癌 ； 預後因素

並列摘要

Background: Cancer is one of the important factors in human deaths.
The statistics of the cause of people death in Taiwan show the topped cause is still the cancer in consecutive thirty years. Lung cancer is at the first place of cancer death, and also globally growing cancer. Therefore, lung cancer has become an urgent need for study. In the recent decades, the study of yeast and drosophila in some cases found that when these creatures have only a single gene mutation, the cells can survive; and when the cells have simultaneous mutation of two genes, this condition will lead to cell death. The relationship of these two genes is called synthetic lethality.
Through the analysis of protein expression by synthetic lethal-associated genes, it would understand the possible relationship between oncogene addition of lung cancer cells and the patient's prognosis. Furthermore to develop a target treatment is expected in the future.
Method: Between 1998 and 2010, a total of 93 patients with lung adenocarcinoma were enrolled in this study. The clinical data are collected and collated. Immunohistochemistry (IHC) staining including 24 paired genes was performed at lung cancer tissue microarray cores of all patients. The IHC result was interpreted by 2 pathologists. Survival curves and the hazard ratio (HR) of incident lung cancer associated with the gene expression during the cohort follow-up were analyzed by statistical methods.
Result: Among 24 paired genes, only FEN1 (Flap endonuclease 1) and RAD54B (RAD54 homolog B) were overexpressed in lung adenocarcinoma patients with poor prognosis. Patients with expression of both FEN1 and RAD54B had significantly poor prognosis (Multivariate analysis: HR=2.35, 95% CI=1.13-4.91, P=0.0230). The 5-year survival rate was also significantly lower in patients with expression of both genes when compared with the other groups with only single gene expression. These results suggested that combined overexpression of FEN1 and RAD54B might be an independent marker for poor prognosis in patients with lung adenocarcinoma.
Conclusion: The overexpression of FEN1 and RAD54B in poorly prognostic lung adenocarcinoma suggests that these two genes might be potential markers for selecting patients at high risk and could be used in the development of effective personalized therapy.

並列關鍵字

FEN1 ； RAD54B

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