比較卵巢癌病患化療敏感性族群和化療抗藥性族群間的基因表現量差異

Abstract

本論文的研究目的是將卵巢癌病患分為兩個族群:化療敏感性(Chemo -sensitive)和化療抗藥性(Chemo - resistant)，比較兩個族群間十個基因表現量的差異，以及利用計算風險分數(Risk score)和總體得分(Overall score)，評估這樣的計分方式是否能夠作為預測卵巢上皮細胞癌的化療反應和預後之指標。 研究共收集149位卵巢癌病患的組織檢體，包含75位化療敏感性(Chemo -sensitive)的卵巢癌病患和74位化療抗藥性(Chemo - resistant)的卵巢癌病患，紀錄患者的臨床病理特徵，並利用即時定量聚合酶連鎖反應(Quantitative real-time polymerase chain reaction, QRT-PCR)偵測十個基因的表現量，十個基因包括: GPC1、CYPB、MSLN、LIMK2、DOCK4、STK31、IGF1、CHI3L1、Survivin、CBAP。另外，利用計算病患的風險分數(Risk score)和總體得分(Overall score)評估病患對於化療反應(Chemo-response)、疾病復發(Disease relapse)和存活狀況(Disease-related death)的相關性，最後進一步分析總體得分的高低與病患的五年無病存活期(Disease free survival, DFS)和整體存活期(Overall survival, OS)之關聯性。 研究結果顯示在化療抗藥性族群之10個基因表現量皆比化療敏感性族群高，並在病患的風險分數和總體得分的分析中，發現化療抗藥性族群的總體得分分佈要較化療敏感性族群高。驗證得到以總體得分的計分方式對於化療反應(Chemo-response)、疾病復發(Disease relapse)和存活狀況(Disease-related death)的 鑑別性是好的。也觀察到當總體得分高的時候，會有較差的無病存活期和整體存活期。 總體而言，應用總體得分的計分方式，當總體得分愈高，病患的預後愈差，因此，可以作為有發展潛能的生物指標，用來預測卵巢癌的化療反應和預後。

The purpose of the study was to compare the genetic expression in ovarian cancer between chemo-sensitive and chemo-resistant groups. In addition, evaluating whether the scoring method calculating the risk score and overall score could be a biomarker of chemo-response and prognosis in ovarian cancer. Total 147 ovarian cancer patients were enrolled in this study, including 75 patient of chemo-sensitive and 74 patients of chemo-resistant. We collected clinicopathological characteristics of patients and determined genetic expression by Quantitative real-time polymerase chain reaction (QRT-PCR).There are ten genes, including GPC1, CYPB, MSLN, LIMK2, DOCK4, STK31, IGF1, CHI3L1, Survivin, CBAP. In addition, evaluating correlations between chemo-response, disease relapse, and disease-related death by calculating the risk score and overall score. Then, we analyzed the relationship between overall score, disease free survival(DFS) and overall survival(OS) further. The genetic expression of patient in chemo-resistant group was higher than in chemo-sensitive group. The distribution of overall score was also higher in chemo- resistant group than in chemo-sensitive group. Good correlations between overall score, chemo-response, disease relapse, and disease-related death by scoring method. Patients with higher overall score had a shorter disease free survival(DFS) and overall survival(OS). These results suggest that the patients with higher overall score had worse clinical outcome. Therefore, scoring system for calculating the overall score of clinical risk evaluation shows potential to predict the chemo-response and outcome in ovarian cancer.