第九型碳酸酐酶之表現及基因多型性與攝護腺癌及腫瘤標記PSA之相關性探討

Study the correlation of carbonic anhydrase 9 expression and genetic polymorphisms with PSA level in patient with prostate cancer

林嘉彥(Chia-Yen Lin)

指導教授 ： 楊順發

中山醫學大學/醫學院/醫學研究所/博士(2020年)

https://doi.org/10.6834/csmu202000071

摘要

在低風險的攝護腺癌患者，我們常以積極追蹤作為治療方式，但找出預防疾病惡化的方法就成為很重要的目標。第九型碳酸酐酶 (Carbonic anhydrase 9, CA9) 在細胞黏附與細胞間的溝通都扮演重要的角色，也因此影響到腫瘤細胞的轉移。本研究目標即探索CA9之基因多型性在攝護腺癌之臨床病理特徵及預後之影響。本研究總計納入579名攝護腺癌並接受機械手臂輔助攝護腺根除手術之受試者。其中270名為初始攝護腺特異抗原 ≤10 ng/ml之病患，而其餘309名病患則為初始攝護腺特異抗原 >10 ng/ml之組別。針對CA9基因的3個位置之多型性，使用做即時聚合酶連鎖反應來分析檢驗。本研究經平衡其他干擾因子後，我們發現個體於CA9 rs3829078含至少一G allele相較於wild-type會有2.241倍的機率其初始攝護腺特異抗原低於10 ng/ml。除此之外，在初始攝護腺特異抗原≤10 ng/ml的病患中，於CA9 rs3829078包含至少一個G allele者分別有4.532及3.484倍的機率罹患淋巴轉移及淋巴血管侵犯。同時，在美國癌症基因體圖譜計畫 (The Cancer Genome Atlas, TCGA) 的資料中也顯示，在初始攝護腺特異抗原≤10 ng/ml的病患CA9 mRNA的表現會顯著的增加淋巴轉移的風險及有趨勢擁有較差的整體存活。本研究之結論如下，CA9基因之rs3829078基因多型性可以預測在初始攝護腺特異抗原≤10 ng/ml的病患之淋巴轉移風險。這是第一個探討CA9基因多型性及CA9之mRNA表現與早期攝護腺癌之關聯性的研究。

關鍵字

第九型碳酸酐酶 ； 基因多型性 ； 攝護腺癌 ； 攝護腺特異抗原

並列摘要

Active surveillance is a common management method for low-risk prostate cancer (CaP). However, devising a method to prevent disease progression is crucial. Carbon anhydrase 9 (CA9) plays a vital role in cell adhesion and intercellular communication correlated to tumor metastasis. Our study explored the impact of CA9 genetic polymorphism on the clinicopathological features and prognosis of CaP. In total, 579 patients with CaP who underwent robot-assisted radical prostatectomy were enrolled, 270 of whom had an initial prostate-specific antigen (PSA) level ≤10 ng/ml and 309 had initial one >10 ng/ml. Three single-nucleotide polymorphisms of CA9 gene were examined using real-time polymerase chain reaction assay. After adjusting the confounding factors, participants carrying at least one G allele at CA9 rs3829078 had a 2.241-fold change in PSA compared with the wild-type carrier (AA), leading to an initial PSA level of ≤10 ng/ml. Furthermore, patients with CaP with an initial PSA level ≤10 ng/ml who carried at least one G allele at CA9 rs3829078 had a 4.532-fold and 3.484-fold risk of lymph node metastasis and lymphovascular invasion, respectively. Moreover, The Cancer Genome Atlas database showed that in CaP patients with an initial PSA level ≤10 ng/ml CA9 mRNA expression significantly increased N1 disease risk and worsened overall survival trends. The rs3829078 polymorphic genotype of CA9 can predict the risk of lymph node metastasis of CaP with an initial PSA level ≤10 ng/ml. This is the first study to report a correlation between CA9 gene polymorphisms/CA9 mRNA expression and early detection of CaP.

並列關鍵字

Carbonic anhydrase 9 ； Polymorphism ； Prostate cancer ； Prostate-specific antigen

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