鼻咽癌病人去毒蛋白基因多型性的預後價值

Prognostic Values of Polymorphisms in Detoxification Proteins for Nasopharyngeal Carcinoma Patients

呂育豪(Yu-Hao Lu) ； 楊昭輝(Chao-Hui Yang) ； 吳靖農(Ching-Nung Wu) ； 黃奕文(Yi-Wen Huang) ； 黃仲鋒(Chung-Feng Hwang)

《台灣耳鼻喉頭頸外科雜誌》 54卷3期 (2019/09) Pp. 134-141

https://doi.org/10.6286/jtohns.201909_54(3).134

摘要

背景：去毒蛋白質和基因在消除内源性和外源性有毒物質（如代謝物、藥物和致癌物）方面發揮著重要作用。本研究的目的是探討在鼻咽癌病人其去毒蛋白基因的多型性的表達及預後相關性。方法：我們收集61件鼻咽癌組織或血液樣本，評估血液DNA在MDR1、CYP3A4和UGT1A7多型性表現，用腫瘤組織切片進行免疫組織染色，分析評估P-glycoprotein的表達。結果：其中29例進行血液分析血中的MDR1、CYP3A4和UGT1A7基因多型性，35例進行免疫組織染色。MDR1基因較重要的SNP位置-G2677T及C3435T有變異者佔76％（22/29）和72％（21/29），CYP3A4基因測定-C653G有變異者佔66％（19/29），UGT1A7基因測定的核酸變異點-T622C變異者佔14％（4/29）。與鼻咽癌臨床預後分析發現MDR1-C3435T變異者Kaplan-Meier存活率分析顯示預後較佳（p = 0.02）。另有35件鼻咽癌檢體接受免疫組織染色，結果顯示MDR1基因相關P-glycoprotein在免疫組織染色陽性者占23％（8/35），並且與鼻咽癌的臨床表現分析，發現P-glycoprotein陽性者多為T3-4及晚期（stage III and IV）鼻咽癌，Kaplan-Meier存活時間也明顯低於陰性者（p = 0.01）。結論：常用的臨床分期通常對預測鼻咽癌病人的預後具有一定的價值，但仍需要新的標記預測腫瘤的侵襲性行為，我們初步發現MDR1基因多型性和P-glycoprotein可能是預測鼻咽癌預後的有用分子標記物。

關鍵字

polymorphisms ； multidrug resistance 1 ； CYP3A4 ； UGT1A7 ； nasopharyngeal neoplasms（多型性 ； 抗多藥物基因 ； CYP3A4 ； UGT1A7 ； 鼻咽癌）

並列摘要

BACKGROUND: Detoxification protein and genes play essential roles in the elimination of endogenous and exogenous toxic substances, such as metabolites, drugs and carcinogens. The purpose of this study was to investigate the expression and prognostic significance of polymorphisms in detoxification genes for nasopharyngeal carcinoma (NPC) patients. METHOD: We collect 61 samples of NPC tissue or blood. The DNAs of blood were assessed for MDR1, CYP3A4 and UGT1A7 polymorphism. The expression of P-glycoprotein was evaluated with immunohistochemical analysis of archived pretreatment tumor materials. RESULTS: The results of DNA of NPC blood indicated that variation incidence of single nucleotide polymorphism (SNP) at MDR1- G2677T, MDR1-C3435T, CYP3A4-C653G and UGT1A7-T622C are 22/29, 21/29, 19/29 and 4/29 respectively. Comparing the clinicopathological parameters, the MDR1-C3435T variation was related to a better overall survival by Kaplen-Meier method (p = 0.02 by log-rank test). Immunohistochemical analysis of P-glycoprotein expression was performed 35 samples of NPC. Positive expression of P-glycoprotein was correlated with T3-4, late stage NPC and poor prognosis (Kaplen-Meier method, p = 0.01 by log-rank test). CONCLUSIONS: Commonly used clinical stage is often of some value in predicting the outcome of patients with NPC, but new parameters are still required for better definition of the aggressiveness of this tumor. We preliminarily find MDR1 gene polymorphism and P-glycoprotein expression may be useful molecular markers to predict prognosis in NPC.

並列關鍵字

polymorphisms ； multidrug resistance 1 ； CYP3A4 ； UGT1A7 ； nasopharyngeal neoplasms