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三重基序(TRIM)47表达增加是人类前列腺癌的不良预后预测指标。

Increased Expression of Tripartite Motif (TRIM) 47 Is a Negative Prognostic Predictor in Human Prostate Cancer.

作者信息

Fujimura Tetsuya, Inoue Satoshi, Urano Tomohiko, Takayama Kenich, Yamada Yuta, Ikeda Kazuhiro, Obinata Daisuke, Ashikari Daisaku, Takahashi Satoru, Homma Yukio

机构信息

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

Department of Geriatric Medicine, Graduate School of Medicine, University of Tokyo, Tokyo, Japan; Department of Anti-Aging Medicine, Graduate School of Medicine, University of Tokyo, Tokyo, Japan; Division of Gene Regulation and Signal Transduction, Research Center for Genomic Medicine, Saitama, Japan.

出版信息

Clin Genitourin Cancer. 2016 Aug;14(4):298-303. doi: 10.1016/j.clgc.2016.01.011. Epub 2016 Jan 28.

Abstract

BACKGROUND

Many prognostic biomarkers associated with androgen signaling have been proposed in PC. The role of tripartite motif (TRIM) proteins remains unclear in PC. We investigated TRIM protein 47 (TRIM47) expression levels in human prostate tissues.

METHODS

We performed immunohistochemistry using original TRIM47 antibody in prostate tissues obtained by radical prostatectomy (n = 105). Stained slides were evaluated for the proportion and staining intensity of immunoreactive cells. Total immunoreactivity (IR) scores (range, 0-8) were calculated as the sum of the proportion and intensity scores. TRIM47 expression levels were confirmed by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Associations between the clinicopathologic features of the patients and their TRIM47 status were analyzed.

RESULTS

Western blot analysis validated the specificity of the anti-TRIM47 antibody in 293T cells. TRIM47 expression levels were found to be significantly increased in PC compared to benign tissues by both immunohistochemistry (P < .0001) and qRT-PCR (P = .003). Additionally, advanced pathologic stage (≥ T3b) was found to be associated with high TRIM47 IR scores (≥ 4; P = .04). Furthermore, high TRIM47 IR scores were also significantly correlated with worse cancer-specific survival rates in multivariate regression analyses (hazard ratio, 6.82; P = .016).

CONCLUSION

The results of the present study indicated differential TRIM47 expression levels in human prostate tissues compared to benign tissues. Because high levels of TRIM47 expression were found to be a strong prognostic factor in PC, TRIM47 may represent a novel therapeutic target.

摘要

背景

在前列腺癌(PC)中已提出许多与雄激素信号相关的预后生物标志物。三联基序(TRIM)蛋白在PC中的作用仍不清楚。我们研究了人前列腺组织中TRIM蛋白47(TRIM47)的表达水平。

方法

我们使用原始的TRIM47抗体对通过根治性前列腺切除术获得的前列腺组织(n = 105)进行免疫组织化学分析。对染色的玻片评估免疫反应性细胞的比例和染色强度。计算总免疫反应性(IR)评分(范围为0 - 8),即比例评分与强度评分之和。通过定量逆转录聚合酶链反应(qRT-PCR)确认TRIM47的表达水平。分析患者的临床病理特征与其TRIM47状态之间的关联。

结果

蛋白质免疫印迹分析验证了抗TRIM47抗体在293T细胞中的特异性。通过免疫组织化学(P <.0001)和qRT-PCR(P =.003)发现,与良性组织相比,PC中TRIM47的表达水平显著升高。此外,发现晚期病理分期(≥ T3b)与高TRIM47 IR评分(≥ 4;P =.04)相关。此外,在多变量回归分析中,高TRIM47 IR评分也与较差的癌症特异性生存率显著相关(风险比,6.82;P =.016)。

结论

本研究结果表明,与良性组织相比,人前列腺组织中TRIM47的表达水平存在差异。由于发现TRIM47的高表达水平是PC的一个强有力的预后因素,TRIM47可能代表一个新的治疗靶点。

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