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良性与恶性前列腺组织之间蛋白质丰度比的差异放射性定量:膜联蛋白A3与癌症的关联

Differential radioactive quantification of protein abundance ratios between benign and malignant prostate tissues: cancer association of annexin A3.

作者信息

Wozny Wojciech, Schroer Klaus, Schwall Gerhard P, Poznanović Slobodan, Stegmann Werner, Dietz Klaus, Rogatsch Hermann, Schaefer Georg, Huebl Heidi, Klocker Helmut, Schrattenholz André, Cahill Michael A

机构信息

ProteoSys AG, Mainz, Germany.

出版信息

Proteomics. 2007 Jan;7(2):313-22. doi: 10.1002/pmic.200600646.

Abstract

A differential quantitative protein expression study, comparing matched prostate cancerous and benign tissues from 31 patients, revealed proteins newly associated with prostate cancer. Average effects for 17 proteins whose abundance was significantly different (p<0.01) across patients ranged from 1.5- to 6.1-fold, and included a number of known cancer markers. The most differentially abundant proteins between cancer and benign samples were isopeptidase T, serum amyloid P (SAP), annexin A3 (ANXA3) and mitochondrial enoyl coenzyme-A hydratase. SAP is restricted to stroma in healthy tissue, and the lower abundance in tumours may be explained by the reduced stromal content. ANXA3 is present in healthy epithelial cells, exhibits strong staining in precancerous prostatic intraepithelial neoplasia, and is relatively less abundant in individual tumour cells of increasing Gleason pattern (GP), despite exhibiting higher overall tissue abundance in tumours. ANXA3 staining was predominantly cytoplasmic, yet nuclear localization was also observed. Strongly staining single cells, possibly phagocytes, were interspersed in highly dedifferentiated GP5 tumour areas among tumour cells without measurable ANXA3. Local recurrent androgen ablation therapy-resistant tumours exhibit heterogenous low levels of ANXA3 staining. Results are discussed focussing on the potential implications for tumour tissues.

摘要

一项差异定量蛋白质表达研究比较了31例患者配对的前列腺癌组织和良性组织,发现了与前列腺癌新相关的蛋白质。17种蛋白质在患者中的丰度存在显著差异(p<0.01),其平均效应范围为1.5至6.1倍,其中包括一些已知的癌症标志物。癌症样本和良性样本中差异最显著的蛋白质是异肽酶T、血清淀粉样蛋白P(SAP)、膜联蛋白A3(ANXA3)和线粒体烯酰辅酶A水合酶。SAP在健康组织中仅限于基质,肿瘤中其丰度较低可能是由于基质含量减少所致。ANXA3存在于健康的上皮细胞中,在癌前前列腺上皮内瘤变中显示强染色,尽管在肿瘤中总体组织丰度较高,但在Gleason分级模式(GP)增加的单个肿瘤细胞中相对含量较低。ANXA3染色主要位于细胞质,但也观察到核定位。在无ANXA3可测量的肿瘤细胞中,强染色的单个细胞(可能是吞噬细胞)散布在高度去分化的GP5肿瘤区域。局部复发性雄激素消融治疗耐药肿瘤表现出异质性低水平的ANXA3染色。本文围绕这些结果对肿瘤组织的潜在影响进行了讨论。

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