Serum prosaposin levels are increased in patients with advanced prostate cancer

Serum prosaposin levels are increased in patients with advanced prostate cancer
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DOI:
10.1002/pros.21427
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发表时间:
2012-02-01
期刊:
影响因子:
2.8
通讯作者:
Vessella, Robert L.
Vessella, Robert L.
中科院分区:
医学3区
文献类型:
--
作者:
Koochekpour, Shahriar;Hu, Siyi;Vessella, Robert L.

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我们之前从转移性去势抵抗性前列腺癌(mCRPCa)细胞中克隆了prosaposin (PSAP),并证明其基因组扩增和/或在转移性前列腺癌细胞系、异种移植物和淋巴结转移中过表达。原发性或晚期前列腺癌中血清PSAP水平及其组织表达的临床组织病理学意义及其与预测或预后变量的关联尚不清楚。我们通过免疫组织化学染色检测了PSAP在前列腺早期胚胎发育过程中的表达,并在包括266个良性和恶性前列腺组织的大型组织芯片中进行了检测。此外,通过ELISA测定了年龄调整后的正常男性人群、154名正常个体和原发性或mCRPCa患者的血清PSAP水平。单因素和多因素分析显示PSAP表达与临床II期和III期肿瘤、显性Gleason模式3和4以及精囊浸润呈显著负相关。在正常男性人群中,血清PSAP水平在青春期前最低,在生育年龄最大的年龄组(20- 39岁)达到峰值,然后在40岁以上的男性中下降到两组之间的范围。无论年龄大小,与正常人相比,原发性器官局限性PCa患者血清PSAP水平显著降低,而mcrpca患者血清PSAP水平升高。我们的研究结果表明,PSAP具有区分原发性和晚期前列腺癌的潜力。需要更多的大规模研究来确定组织表达或血清PSAP水平作为前列腺癌的诊断或预后标志物或治疗靶点的有效性。中华医学杂志(英文版),2012。(C) 2011 Wiley期刊公司
BACKGROUND We previously cloned prosaposin (PSAP) from metastatic castrate-resistant prostate cancer (mCRPCa) cells and demonstrated its genomic amplification and/or overexpression in metastatic PCa cell lines, xenografts, and lymph node metastases. The clinicohistopathological significance of serum PSAP levels and its tissue expression and association with predictive or prognostic variable in primary or advanced PCa are not known.METHODS. We examined PSAP expression by immunohistochemical staining during early embryogenic development of the prostate and within a large tissue microarray which included 266 benign and malignant prostate tissues. In addition, serum PSAP levels in the age-adjusted normal male population and in 154 normal individuals and patients with primary or mCRPCa were measured by an ELISA assay.RESULTS. Univariate and multivariate analyses revealed a significant and inverse association between PSAP expression and clinical stages II and III tumors, dominant Gleason patterns 3 and 4, and seminal vesicle invasion. In the normal male population, the lowest serum PSAP level was detected before puberty, peaked at the most reproductive age group (20- to 39-year old), and then, decreased to a range between the two groups for men above 40-year old. Regardless of age and when compared with normal individuals, serum PSAP levels significantly decreased in primary organ-confined PCa, but increased in those with mCRPCa.CONCLUSION. Our results show that PSAP has the potential to differentiate between primary and advanced PCa. Additional large-scale studies are needed to define the usefulness of tissue expression or serum PSAP levels as a diagnostic or prognostic marker or as a therapeutic target in PCa. Prostate 72: 253-269, 2012. (C) 2011 Wiley Periodicals, Inc.