α型葉酸接受體的高表現量與漿液性卵巢癌較差存活率相關

Abstract

目標： 這個研究是為了瞭解漿液性(serous)卵巢癌的病人在臨床病理特徵中α型葉酸接受體(alpha-folate receptor, α-FR)的表現量與病人的預後兩者之間關聯性。 方法： 使用半定量反轉錄聚合酵素連鎖反應(Semi-quantitative reverse-transcription polymerase chain reaction)的方法去偵測91位漿液性卵巢癌病人，其腫瘤組織中α型葉酸接受體(α-FR)表現的程度。除此之外，更分析病人其它臨床病理因素與生物指標，包括國際婦產科聯盟的臨床期別(FIGO stage)、腫瘤惡性程度(tumor grade)、是否接受理想的減積手術(optimal surgery)、淋巴結轉移(lymph nodes metastasis)、術前血清中CA-125的表現量(pre-operative CA-125)以及α型葉酸接受體(α-FR)在癌化組織中的表現量。再將這些結果與病人的無癌症復發期(disease-free interval, DFI)及整體存活率(overall survival, OS)做進一步的分析。 結果： 有4、6、65與16位病人分別位於卵巢癌分期中的第I、第II、第III與第IV期，其中44%的病人受過理想腫瘤減積手術(optimal debulking surgery)治療。末期(stage I: 0.451, stage II: 0.415, stage III: 0.652, 和stage IV: 0.768, p=0.004)或是無法接受理想減積手術(sub-optimal debulking surgery，optimal: 0.490, sub-optimal: 0.766, p=0.003)的病人，其癌症組織中比初期或是接受理想腫瘤減積手術(optimal cyto-reductive surgery)的病人具有明顯較高的α型葉酸接受體表現量。而在預後的分析中，利用多變數分析發現α型葉酸接受體(α-FR)的高表現量對於無癌症復發期(disease-free interval,DFI)是一個明顯的較差的預後因子(HR: 2.70 (1.20-6.05), p=0.016)。對於整體存活率(overall survival,OS)而言則具有邊緣性顯著差異的負面影響(HR: 3.51 (0.93-13.29), p=0.065)。 結論： 漿液性卵巢癌的病人若是在腫瘤檢體上反映出較高的α型葉酸接受體(α-FR)表現量，就可能會有較短的無癌症復發期(disease-free interval, DFI)與整體存活率(overall survival, OS)。因此，α型葉酸接受體(α-FR)對於治療卵巢癌來說可能是一個有發展潛力的生物標記及標靶治療的標的。 關鍵字：α型葉酸接受體、腫瘤抗原標記CA-125、漿液性卵巢癌、存活率

Objectives: To investigate the relationship between alpha-folate receptor (α-FR) expression levels to the clinico-pathologic features and outcomes of patients with serous ovarian carcinoma. Methods: Semi-quantitative reverse-transcription polymerase chain reaction detected α-FR expression in 91 patients with serous ovarian carcinoma. Clinico-pathologic parameters and biomarkers, including FIGO stage, tumor grade, optimal surgery, lymph nodes metastasis, pre-operative serum CA-125, and α-FR expression levels in cancerous tissues to evaluate disease-free interval (DFI) and overall survival (OS), were analyzed. Results: There were 4, 6, 65, and 16 patients with stages I, II, III, and IV ovarian carcinoma, respectively. Forty (44%) underwent optimal debulking surgery. Patients with advanced stages (stage I: 0.451, stage II: 0.415, stage III: 0.652, stage IV: 0.768, p=0.004) or those with sub-optimal debulking surgery (optimal: 0.490, sub-optimal: 0.766, p=0.003) had significantly higher α-FR expression levels compared to those with early stages or optimal debulking surgery. In prognostic analysis, high α-FR expression level (HR: 2.70 (1.20-6.05), p=0.016) was an independent poor prognostic factor for DFI and had a negative impact on OS with marginal significance (HR: 3.51 (0.93-13.29), p=0.065) using multivariate analyses. Conclusions: Patients of serous ovarian carcinoma with high α-FR expression in cancerous tissue have shorter DFI and OS. α-FR may be a potential biomarker for predicting the outcome of serous ovarian carcinoma patients. Key words: alpha-folate receptor, CA-125, ovarian serous carcinoma, survival