探討LIGHT與上皮性卵巢癌病人預後的相關性

The Correlation of LIGHT and The Outcome of Epithelial Ovarian Carcinoma Patients

黃奕堯(Yi-Yao Huang)

指導教授 ： 李建南

共同指導教授 ： 鄭文芳(Wen-Fang Chang)

國立臺灣大學/醫學院/分子醫學研究所/碩士(2015年)

https://doi.org/10.6342/NTU.2015.00671

摘要

研究目標
　　測量HVEM、LIGHT及BTLA的表現量與上皮性卵巢癌病人預後的關聯性。
研究材料與方法
　　使用反轉錄聚合酵素連鎖反應(Reverse-transcription polymerase chain reaction, RT-PCR)和即時定量聚合酶鏈鎖反應(real-time quantitative reverse-transcription polymerase chain reaction, RTQ RT-PCR)的方法去偵測上皮性卵巢癌病人中HVEM、LIGHT、BTLA的表現程度。我們統計病人的臨床病理結果與生物指標，包括癌症的期別(disease stage)、病理組織型態(histology)、腫瘤惡性程度(tumor grade)、是否接受理想的減積手術(optimal debulking surgery)、病人術後化學治療療效 (chemotherapeutic response)以及HVEM、LIGHT及BTLA在癌組織中的表現量。再將這些因子與病人的無癌症復發期(disease-free survival)及整體存活率(overall survival)做進一步的分析。
研究結果
在所有254個上皮性卵巢癌的病人當中，平均年齡為53.3歲。其中有61位為早期卵巢癌病人，193位為晚期卵巢癌病人。57.8%的病人其病理組織型態為漿液性(serous)卵巢癌。全部病人的組織檢體中皆有LIGHT表現，但僅有154人檢測到有表現BTLA。在預後分析中，利用多變項統計分析後發現剩餘腫瘤是否大於1 cm (HR:2.9 (1.7-4.8), p<0.001)、LIGHT表現量高(HR:1.6 (1.2-2.1), p=0.001)為整體存活期之預後預測因子。此外，剩餘腫瘤是否大於1 cm (HR: 2.1 (1.5-2.9), p<0.001)、LIGHT表現量高(HR:2.1 (1.7-2.5), p<0.001)亦為無癌症復發期之預後預測因子。
我們將LIGHT表現量高低分組後，計算無癌症復發期及整體存活期之存活曲線。發現LIGHT表現量低的分組較表現量高的分組有較佳的無癌症復發期(Ptrend<0.001)及整體存活期(Ptrend=0.03)。而LIGHT表現量高低與BTLA表現量高低呈現正相關(p<0.001)。我們的研究亦發現，LIGHT表現量高低亦與上皮性卵巢癌病患對術後化療藥物治療反應有關。對化療藥物治療效果較佳(chemo-sensitive)的患者通常有較低的LIGHT表現量(P<0.001)。
研究結論
在卵巢癌腫瘤組織上的LIGHT表現量可以做為預測上皮性卵巢癌患者預後的無癌復發期及整體存活期獨立之預後因子。因此，LIGHT表現量具有潛力用來做為預測卵巢癌預後參考。

關鍵字

卵巢癌預後 ； 腫瘤免疫學 ； HVEM(TNFRSF14) ； LIGHT(TNFSF14) ； BTLA

並列摘要

Objective
To explore the correlation between HVEM、LIGHT and BTLA expression levels in cancerous tissue and the prognosis of patients with epithelium ovarian carcinomas.
Materials and Methods
The expression levels of HVEM、LIGHT、BTLA in epithelial ovarian carcinoma tissue were measured by reverse-transcription polymerase chain reaction, (RT-PCR) and real-time quantitative reverse-transcription polymerase chain reaction (RTQ RT-PCR). Clinico-pathologic parameters and biomarkers including disease stage, histology, tumor grade, surgical status, chemotherapeutic response and HVEM, LIGHT and BTLA expression levels in cancerous tissues were used for prognostic factors to predict the disease-free survival (DFS) and overall survival (OS) of ovarian cancer patients.
Results
The mean age of 254 ovarian cancer patients are 53.3 years old. Sixty-one out of 254 were diagnosed as early ovarian carcinomas while the remaining 193 were as advanced diseases. 57.8% of the studied population were serous ovarian carcinoma. LIGHT could be detected in all the cancerous specimens but BTLA only could be detected in 154 cases. In the multivariate analysis, sub-optimal surgery (residual tumor size > 1 cm) [hazard ratio (HR): 2.9, 95% confidence interval (CI) 1.7-2.8, p<0.001] and higher LIGHT expression levels [HR: 1.6, 95% CI 1.2-2.1, p=0.001] were independent prognostic factors of OS. In addition, sub-optimal surgery (residual tumor size > 1 cm) [HR: 2.1, 95% CI 1.5-2.9, p<0.001] and higher LIGHT expression levels [HR: 2.1, 95% CI 1.7-2.5, p<0.001] were independent prognostic factors of DFS.
According the expression levels of LIGHT in cancerous tissues, the studied could be divided into three groups. In this study, the patients with lower LIGHT expression levels had longer DFS (Ptrend<0.001) and OS (Ptrend=0.03) than those with higher LIGHT expression levels. Furthermore, the LIGHT expression levels positively correlated to the BTLA expression levels (p<0.001) in this study. The tumors in the LIGHT higher expression group were less chemo-seneitive (p<0.001).
Conclusions
The patients with higher LIGHT expression levels in ovarian cancerous tissue would have shorter DFI and OS. The LIGHT expression levels may be a potential biomarker for predicting the prognosis of ovarian cancer patients.

並列關鍵字

ovarian cancer prognosis ； caner-immunology ； HVEM(TNFRSF14) ； LIGHT(TNFSF14) ； BTLA

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