Diagnostic biomarkers of prostate cancer

Diagnostic biomarkers of prostate cancer
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DOI:
10.3109/00365599.2010.526141
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发表时间:
2011-02-01
影响因子:
--
通讯作者:
Egevad, Lars
Egevad, Lars
中科院分区:
其他
文献类型:
--
作者:
Haggarth, Lars;Hagglof, Christina;Egevad, Lars

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Objective.前列腺癌(PC)的诊断组织生物标志物包括基底细胞标志物和α-甲基酰基辅酶A-消旋酶(AMACR),通常组合使用。它们的灵敏度和特异性并不完美,在常规染色切片难以诊断的病例中,需要额外的PC诊断生物标志物。材料和方法。本研究调查了通过在人类蛋白质图谱数据库(www.example.com)中搜索发现的三种新型组织生物标志物对PC的诊断准确性www.proteinatlas.com:体细胞色素c(CYCS)、肠细胞激酶(ICK)和核因子-κ B激酶亚基β(IKBKB)抑制剂,并与AMACR进行比较。从40个连续的根治性前列腺切除术(RP)标本,包括良性前列腺组织,萎缩,高级别前列腺上皮内瘤变(HGPIN)和PC构建组织芯片。根据染色强度和程度对免疫反应性进行评分。实时聚合酶链反应(PCR)进行恶性和良性冷冻组织样本从32 RP标本。结果所有四种生物标志物在PC和HGPIN中的表达均强于良性组织(p < 0.001)。ICK和AMACR对PC的诊断准确率最高,为97%。CYCS、ICK、IKBKB和AMACR的曲线下面积分别为0.859、0.997、0.865和0.983。通过实时荧光定量PCR证实良性和恶性前列腺组织中存在这些基因的mRNA转录本。结论. AMACR是一种准确诊断PC的组织标志物。然而,在某些PC中,AMACR为假阴性,CYCS、ICK和IKBKB可作为辅助诊断工具。
Objective. Diagnostic tissue biomarkers for prostate cancer (PC) include basal cell markers and alpha-methylacyl-coenzyme A-racemase (AMACR), often used in combination. Their sensitivity and specificity are not perfect and there is a need for additional diagnostic biomarkers for PC in cases that are difficult to diagnose on routine stained sections. Material and methods. This study investigated the diagnostic accuracy of three novel tissue biomarkers for PC found through a search in the Human Protein Atlas database (www.proteinatlas.com): somatic cytochrome c (CYCS), intestinal cell kinase (ICK) and inhibitor of nuclear factor-kappa B kinase subunit beta (IKBKB), and compared the results with AMACR. A tissue microarray was constructed from 40 consecutive radical prostatectomy (RP) specimens including benign prostatic tissue, atrophy, high-grade prostatic intraepithelial neoplasia (HGPIN) and PC. Immunoreactivity was scored based on staining intensity and extent. Real-time polymerase chain reaction (PCR) was performed on malignant and benign frozen tissue samples from 32 RP specimens. Results. All four biomarkers showed a stronger expression in PC and HGPIN than in benign tissue (p < 0.001). The highest diagnostic accuracy for PC was achieved with ICK and AMACR at 97%. The area under the curve for CYCS, ICK, IKBKB and AMACR was 0.859, 0.997, 0.865 and 0.983, respectively. The presence of mRNA transcripts of the genes was confirmed by real-time PCR in benign and malignant prostatic tissue. Conclusions. AMACR is an accurate diagnostic tissue marker for PC. However, in some PCs AMACR is false negative and a panel of CYCS, ICK and IKBKB may serve as ancillary diagnostic tool.