- 學位論文
MALAT1之單核苷酸多型性對台灣攝護腺癌的影響
The Impacts of MALAT1 Single-Nucleotide Polymorphisms on Prostate Cancer In Taiwanese
摘要
現有之研究顯示長鏈非編碼 RNA肺腺癌轉移相關之轉錄物1 (MALAT1)可以調節基因的表現，在攝護腺癌的診斷和預後中扮演著重要角色。MALAT1的單核苷酸多型性可以改變多種癌症的腫瘤易感受性，然而目前對MALAT1 單核苷酸多型性與攝護腺癌之間的關聯所知甚少。本研究採集了2012 年至 2017 年579 名接受攝護腺根除手術之攝護腺癌患者血液檢體，共分析三個 MALAT1單核苷酸多型性 (rs3200401、rs619586 和 rs1194338) 與臨床病理表現之關聯性，以釐清MALAT1單核苷酸多型性是否對台灣攝護腺癌產生影響。結果顯示帶有MALAT1單核苷酸多型性rs1194338的患者與淋巴轉移有關 (OR：2.400，95% CI 1.224-4.707，p= 0.009)，尤其是在初始攝護腺特異抗原> 10 ng/ml的患者 (OR：2.544，95% CI 1.189-5.441，p=0.014)；不過帶有MALAT1單核苷酸多型性rs1194338的患者發生神經周圍侵犯的機會也顯著較少 (OR：0.614，95% CI 0.397-0.949，p=0.028)。另一個MALAT1單核苷酸多型性rs619586則和較惡性的格里森分組有關 (OR 1.801，95% CI 1.136-2.856，p=0.012)。總結來說，MALAT1單核苷酸多型性除了與較多的淋巴結轉移和較惡性的Gleason 分級有關之外，也同時具有顯著較低的攝護腺癌神經周圍浸潤，因此MALAT1單核苷酸多型性rs619586 和 rs1194338 的存在可能會改變MALAT1在攝護腺癌的癌變機轉調控。
並列摘要
Plenty of evidence demonstrates that long noncoding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) could regulate genetic expression and play a vital role in both the diagnosis and prognosis of prostate cancer. Single-nucleotide polymorphisms (SNPs) of MALAT1 could alter the oncogenesis in various cancers. However, the associations between MALAT1 SNPs and prostate cancer have poorly evaluated to date. Our study included 579 patients with prostate cancer who received robotic-assisted radical prostatectomy at Taichung Veterans General Hospital from 2012 to 2017. Three MALAT1 SNPs (namely, rs3200401, rs619586, and rs1194338) were analyzed to identify the impacts of SNPs on the clinicopathological features of Taiwanese prostate cancer. The results show that for patients with at least one polymorphic A allele at rs1194338, the risk of pathologic lymph node invasion was significantly increased despite their initial prostate specific antigen (iPSA) level (OR: 2.400, 95% CI 1.224-4.707, p=0.009). This significant association between rs1194338 and node-positive disease was mainly contributed by the cases with iPSA > 10 ng/ml (OR: 2.544, 95% CI 1.189-5.441, p=0.014). On the other hand, patients with rs1194338 presented with less perineural invasion (OR: 0.614, 95% CI 0.397-0.949, p=0.028). Furthermore, patients with polymorphic G allele in rs619586 had a significantly higher risk of advanced Gleason Grade groups (OR 1.801, 95% CI 1.136-2.856, p=0.012). In conclusion, MALAT1 SNPs are significantly associated with susceptibility for more advanced Gleason grade, more nodal metastases, and less perineural invasion in prostate cancer. The presence of MALAT1 SNPs rs619586 and rs1194338 might alter the oncogenesis in prostate cancer.