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功能性单核苷酸重复多态性在 HGF 启动子区域与膀胱癌的风险和恶性侵袭性相关。

Functional mononucleotide repeat polymorphism in the promoter region of HGF is associated with risk and malignant aggressiveness of bladder cancer.

机构信息

Department of Urology, Akita University Graduate School of Medicine, Akita, Japan.

出版信息

Int J Oncol. 2014 Mar;44(3):678-84. doi: 10.3892/ijo.2013.2221. Epub 2013 Dec 20.

Abstract

Increased expression of hepatocyte growth factor (HGF) has been shown to be associated with aggressiveness in several types of cancer. Shorter variants of deoxyadenosine tract element (DATE) located in the HGF promoter region have been reported to enhance the expression of HGF. In this study, we investigated the role of HGF DATE variants in bladder cancer risk, HGF expression and clinicopathological features. The frequency of individuals with a short DATE (<28 repeats) in peripheral blood lymphocytes (PBLs) was significantly higher in bladder cancer patients compared to controls (p<0.001). Somatic mutations were observed in 37 of 70 bladder tumor (BT) tissues and the frequency of mutation to long DATE was significantly higher than that to short DATE (p=0.047). The presence of the short DATE in BT tissue was significantly associated with higher tumor grade (p=0.015). HGF mRNA levels were significantly higher in pT2 tumors than pTa or pT1 tumors (p=0.019), and in grade 3 tumors than grade 1 or 2 tumors (p=0.020). Furthermore, BT tissues with the short DATE showed significantly higher levels of HGF mRNA (p<0.001). In patients who underwent radical cystectomy, those with higher HGF expression had a significantly shorter overall survival than those with lower HGF expression (p=0.012). In conclusion, HGF may be associated with the prognosis of patients who undergo radical cystectomy, and the HGF DATE may affect the risk and aggressiveness of bladder cancer by altering HGF expression.

摘要

已有研究表明,在多种类型的癌症中,肝细胞生长因子(HGF)的表达增加与侵袭性相关。位于 HGF 启动子区域的脱氧腺苷重复序列元件(DATE)的较短变体已被报道可以增强 HGF 的表达。在这项研究中,我们研究了 HGF DATE 变体在膀胱癌风险、HGF 表达和临床病理特征中的作用。与对照组相比,膀胱癌患者外周血淋巴细胞(PBL)中短 DATE(<28 个重复)个体的频率显著更高(p<0.001)。在 70 个膀胱癌(BT)组织中观察到 37 个体细胞突变,长 DATE 的突变频率明显高于短 DATE(p=0.047)。BT 组织中短 DATE 的存在与较高的肿瘤分级显著相关(p=0.015)。与 pTa 或 pT1 肿瘤相比,pT2 肿瘤的 HGF mRNA 水平显著更高(p=0.019),与 3 级肿瘤相比,1 级或 2 级肿瘤的 HGF mRNA 水平显著更高(p=0.020)。此外,具有短 DATE 的 BT 组织的 HGF mRNA 水平显著更高(p<0.001)。在接受根治性膀胱切除术的患者中,HGF 表达较高的患者的总生存期明显短于 HGF 表达较低的患者(p=0.012)。总之,HGF 可能与接受根治性膀胱切除术的患者的预后相关,而 HGF DATE 可能通过改变 HGF 表达来影响膀胱癌的风险和侵袭性。

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