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Sp1在膀胱尿路上皮癌患者中过度表达,并与疾病进展及不良预后相关。

Sp1 is overexpressed and associated with progression and poor prognosis in bladder urothelial carcinoma patients.

作者信息

Zhu Jialiang, Lu Ziwen, Ke Mang, Cai Xianguo

机构信息

Department of Urology, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, No. 150 Ximen Street, Taizhou, 317000, Zhejiang Province, People's Republic of China.

出版信息

Int Urol Nephrol. 2022 Jul;54(7):1505-1512. doi: 10.1007/s11255-022-03212-6. Epub 2022 Apr 25.

DOI:10.1007/s11255-022-03212-6
PMID:35467245
Abstract

BACKGROUND

Specificity protein 1 (Sp1) is a transcription factor that exerts key functions in the carcinogenesis and progression of various types of cancer. However, its expression and prognostic value in bladder urothelial carcinoma (BUC) have yet to be completely elucidated.

METHODS

The present study performed reverse transcription-quantitative polymerase chain reaction (RT-qPCR) to examine Sp1 mRNA expression in 12 pairs of urothelial carcinoma and adjacent normal bladder tissues. Immunohistochemistry (IHC) was performed in 113 paraffin-embedded urothelial carcinoma tissues to detect the expression of Sp1. Kaplan-Meier plots and Cox proportional hazards regression model were used to analyze the correlation between Sp1 expression and patient prognosis.

RESULTS

The mRNA expression of Sp1 was elevated in the urothelial carcinoma by RT-qPCR compared with their paired normal bladder tissues. Among 113 cases of patients with urothelial carcinoma, there were 39 low histological grade and 74 high histological grade, 61 unifocal tumor and 52 multifocal tumor, 78 cases in Ta, T1, and T2 stages, and 35 cases in T3 and T4 stages. The enhanced expression of Sp1 mRNA was observed in tumors with a high histological grade, and invasive and metastatic samples. Immunohistochemistry revealed that Sp1 high expression was significantly correlated with the histological grade, tumor stage, vascular invasion, lymph node metastasis and distant metastasis (P < 0.05). Kaplan-Meier analysis demonstrated that elevated Sp1 expression in cancer tissue was correlated with a significantly poor overall survival (OS) and disease-free survival (DFS) compared with samples with low Sp1 expression (P < 0.05). Multivariate analyses by Cox's proportional hazard model also revealed that the expression of Sp1 was an independent prognostic factor in urothelial carcinoma.

CONCLUSION

Sp1 expression is significantly elevated in urothelial carcinoma and may be used to identify a subset of patients with aggressive behaviors and poor clinical outcomes. Sp1 is a potential novel independent prognostic biomarker for patients with urothelial carcinoma following surgery.

摘要

背景

特异性蛋白1(Sp1)是一种转录因子,在各类癌症的发生和发展过程中发挥关键作用。然而,其在膀胱尿路上皮癌(BUC)中的表达及预后价值尚未完全阐明。

方法

本研究采用逆转录定量聚合酶链反应(RT-qPCR)检测12对尿路上皮癌组织及相邻正常膀胱组织中Sp1 mRNA的表达。对113例石蜡包埋的尿路上皮癌组织进行免疫组织化学(IHC)检测Sp1的表达。采用Kaplan-Meier曲线和Cox比例风险回归模型分析Sp1表达与患者预后的相关性。

结果

RT-qPCR结果显示,尿路上皮癌组织中Sp1的mRNA表达高于配对的正常膀胱组织。113例尿路上皮癌患者中,组织学低级别39例,高级别74例;单灶肿瘤61例,多灶肿瘤52例;Ta、T1和T2期78例,T3和T4期35例。在组织学高级别、侵袭性和转移性肿瘤样本中观察到Sp1 mRNA表达增强。免疫组织化学显示,Sp1高表达与组织学分级、肿瘤分期、血管侵犯、淋巴结转移和远处转移显著相关(P<0.05)。Kaplan-Meier分析表明,与Sp1低表达样本相比,癌组织中Sp1表达升高与总生存期(OS)和无病生存期(DFS)显著较差相关(P<0.05)。Cox比例风险模型的多因素分析还显示,Sp1表达是尿路上皮癌的独立预后因素。

结论

Sp1在尿路上皮癌中的表达显著升高,可用于识别具有侵袭性行为和不良临床结局的患者亚组。Sp1是尿路上皮癌患者术后潜在的新型独立预后生物标志物。

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