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膀胱癌患者尿液和肿瘤组织中生存素mRNA表达的定量分析及其与疾病检测和预后的潜在相关性。

Quantitative analysis of survivin mRNA expression in urine and tumor tissue of bladder cancer patients and its potential relevance for disease detection and prognosis.

作者信息

Weikert Steffen, Christoph Frank, Schrader Mark, Krause Hans, Miller Kurt, Müller Markus

机构信息

Department of Urology, Charitè, Universitaetsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany.

出版信息

Int J Cancer. 2005 Aug 10;116(1):100-4. doi: 10.1002/ijc.21000.

Abstract

Suppression of apoptosis may favor the onset and progression of cancer. Survivin is an inhibitor of apoptosis that has been suggested as a novel diagnostic/prognostic marker of bladder cancer. In this study, survivin mRNA expression was measured by a sensitive real-time PCR assay in tumor tissue and urine from bladder cancer patients and assessed for its potential diagnostic and prognostic relevance. Specimens from 53 patients with bladder transitional cell carcinoma (TCC) were analyzed, the controls being normal urothelial tissues (n = 14) and urine from benign disease patients (n = 22) and healthy individuals (n = 14). Survivin transcripts were commonly detected in tumor tissues, but not in normal urothelium, and increasing mRNA levels correlate with progressing pathologic stage (p = 0.001) and grade categories (p < 0.004). Higher levels of expression were associated with a reduced time to recurrence in noninvasive TCCs (p = 0.027, log-rank test) and a trend toward shorter disease-free survival in muscle-invasive tumors (p = 0.067). Urinary survivin analysis detects TCC with higher sensitivity (68.6%) and equal specificity (100%) when compared with cytology (31.4% and 97.1%). Our results indicate that tissue levels of survivin mRNA predict disease-free survival in noninvasive TCC and may have a role in bladder cancer progression. When analyzed by RT-PCR in urine, survivin is a highly specific biomarker for TCC detection.

摘要

细胞凋亡的抑制可能有利于癌症的发生和发展。生存素是一种细胞凋亡抑制剂,已被认为是膀胱癌的一种新型诊断/预后标志物。在本研究中,通过灵敏的实时PCR测定法测量膀胱癌患者肿瘤组织和尿液中生存素mRNA的表达,并评估其潜在的诊断和预后相关性。分析了53例膀胱移行细胞癌(TCC)患者的标本,对照组为正常尿路上皮组织(n = 14)、良性疾病患者的尿液(n = 22)和健康个体的尿液(n = 14)。生存素转录本在肿瘤组织中普遍检测到,但在正常尿路上皮中未检测到,且mRNA水平升高与病理分期进展(p = 0.001)和分级类别(p < 0.004)相关。较高的表达水平与非侵袭性TCC复发时间缩短相关(p = 0.027,对数秩检验),在肌肉侵袭性肿瘤中无病生存期缩短有趋势(p = 0.067)。与细胞学检查(31.4%和97.1%)相比,尿液生存素分析检测TCC具有更高的敏感性(68.6%)和相同的特异性(100%)。我们的结果表明,生存素mRNA的组织水平可预测非侵袭性TCC的无病生存期,并可能在膀胱癌进展中起作用。当通过RT-PCR在尿液中进行分析时,生存素是检测TCC的高度特异性生物标志物。

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