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探索前列腺癌基因组发现,在根治性前列腺切除术后前列腺特异抗原复发的患者中,PTEN、FAS和PAPSS2同时缺失。

Exploring prostate cancer genome reveals simultaneous losses of PTEN, FAS and PAPSS2 in patients with PSA recurrence after radical prostatectomy.

作者信息

Ibeawuchi Chinyere, Schmidt Hartmut, Voss Reinhard, Titze Ulf, Abbas Mahmoud, Neumann Joerg, Eltze Elke, Hoogland Agnes Marije, Jenster Guido, Brandt Burkhard, Semjonow Axel

机构信息

Prostate Center, Department of Urology, University Hospital Muenster, Albert-Schweitzer-Campus 1, Gebaeude 1A, Muenster D-48149, Germany.

Center for Laboratory Medicine, University Hospital Muenster, Albert-Schweitzer-Campus 1, Gebaeude 1A, Muenster D-48149, Germany.

出版信息

Int J Mol Sci. 2015 Feb 11;16(2):3856-69. doi: 10.3390/ijms16023856.

Abstract

The multifocal nature of prostate cancer (PCa) creates a challenge to patients' outcome prediction and their clinical management. An approach that scrutinizes every cancer focus is needed in order to generate a comprehensive evaluation of the disease, and by correlating to patients' clinico-pathological information, specific prognostic biomarker can be identified. Our study utilized the Affymetrix SNP 6.0 Genome-wide assay to investigate forty-three fresh frozen PCa tissue foci from twenty-three patients. With a long clinical follow-up period that ranged from 2.0-9.7 (mean 5.4) years, copy number variation (CNV) data was evaluated for association with patients' PSA status during follow-up. From our results, the loss of unique genes on 10q23.31 and 10q23.2-10q23.31 were identified to be significantly associated to PSA recurrence (p < 0.05). The implication of PTEN and FAS loss (10q23.31) support previous reports due to their critical roles in prostate carcinogenesis. Furthermore, we hypothesize that the PAPSS2 gene (10q23.2-10q23.31) may be functionally relevant in post-operative PSA recurrence because of its reported role in androgen biosynthesis. It is suggestive that the loss of the susceptible region on chromosome 10q, which implicates PTEN, FAS and PAPSS2 may serve as genetic predictors of PSA recurrence after radical prostatectomy.

摘要

前列腺癌(PCa)的多灶性给患者的预后预测及其临床管理带来了挑战。需要一种仔细检查每个癌灶的方法,以便对该疾病进行全面评估,并通过与患者的临床病理信息相关联,来识别特定的预后生物标志物。我们的研究利用Affymetrix SNP 6.0全基因组检测方法,对来自23名患者的43个新鲜冷冻PCa组织灶进行了研究。在长达2.0 - 9.7(平均5.4)年的临床随访期内,评估了拷贝数变异(CNV)数据与患者随访期间前列腺特异性抗原(PSA)状态的相关性。从我们的结果来看,10q23.31和10q23.2 - 10q23.31上独特基因的缺失被确定与PSA复发显著相关(p < 0.05)。PTEN和FAS缺失(10q23.31)的影响支持了先前的报道,因为它们在前列腺癌发生过程中起关键作用。此外,我们推测PAPSS2基因(10q23.2 - 10q23.31)可能在术后PSA复发中具有功能相关性,因为据报道它在雄激素生物合成中发挥作用。这表明10号染色体q臂上的易感区域缺失,涉及PTEN、FAS和PAPSS2,可能作为根治性前列腺切除术后PSA复发的遗传预测指标。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3630/4346930/6f74c000eea3/ijms-16-03856-g001.jpg

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