Background Prostate cancer (PCa) is the most frequently diagnosed non-skin cancer and a leading cause of mortality among males in developed countries. However, our understanding of the global changes of protein complexes within PCa tissue specimens remains very limited, although it has been well recognized that protein complexes carry out essentially all major processes in living organisms and that their deregulation drives the pathogenesis and progression of various diseases. Methods By coupling tandem mass tagging-synchronous precursor selection-mass spectrometry/mass spectrometry/mass spectrometry with differential expression and co-regulation analyses, the present study compared the differences between protein complexes in normal prostate, low-grade PCa, and high-grade PCa tissue specimens. Results Globally, a large downregulated putative protein-protein interaction (PPI) network was detected in both low-grade and high-grade PCa, yet a large upregulated putative PPI network was only detected in high-grade but not low-grade PCa, compared with normal controls. To identify specific protein complexes that are deregulated in PCa, quantified proteins were mapped to protein complexes in CORUM (v3.0), a high-quality collection of 4274 experimentally verified mammalian protein complexes. Differential expression and gene ontology (GO) enrichment analyses suggested that 13 integrin complexes involved in cell adhesion were significantly downregulated in both low- and high-grade PCa compared with normal prostate, and that four Prothymosin alpha (ProTα) complexes were significantly upregulated in high-grade PCa compared with normal prostate. Moreover, differential co-regulation and GO enrichment analyses indicated that the assembly levels of six protein complexes involved in RNA splicing were significantly increased in low-grade PCa, and those of four subcomplexes of mitochondrial complex I were significantly increased in high-grade PCa, compared with normal prostate. Conclusions In summary, to the best of our knowledge, the study represents the first large-scale and quantitative, albeit indirect, comparison of individual protein complexes in human PCa tissue specimens. It may serve as a useful resource for better understanding the deregulation of protein complexes in primary PCa.

中文翻译：

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前列腺组织标本的定量蛋白质组学分析确定了原发性前列腺癌中失调的蛋白质复合物。

背景 前列腺癌 (PCa) 是最常被诊断出的非皮肤癌，也是发达国家男性死亡的主要原因。然而，我们对 PCa 组织标本中蛋白质复合物的整体变化的理解仍然非常有限，尽管众所周知，蛋白质复合物在生物体中基本上完成了所有主要过程，并且它们的失调驱动了各种疾病的发病机制和进展。方PCa 组织标本。结果在全球范围内，与正常对照相比，在低级别和高级别 PCa 中都检测到一个大的下调的假定蛋白质 - 蛋白质相互作用 (PPI) 网络，但一个大的上调的假定 PPI 网络仅在高级而不是低级别 PCa 中检测到. 为了识别在 PCa 中失调的特定蛋白质复合物，将量化的蛋白质映射到 CORUM (v3.0) 中的蛋白质复合物，这是 4274 个经过实验验证的哺乳动物蛋白质复合物的高质量集合。差异表达和基因本体 (GO) 富集分析表明，与正常前列腺相比，低级别和高级别 PCa 中参与细胞粘附的 13 个整合素复合物显着下调，而高级别前列腺癌中 4 个原胸腺素 α (ProTα) 复合物显着上调。 - 级 PCa 与正常前列腺相比。而且，差异共调节和 GO 富集分析表明，与 RNA 剪接有关的六种蛋白质复合物的组装水平在低级别 PCa 中显着增加，而线粒体复合物 I 的四个亚复合物在高级 PCa 中的组装水平显着增加，与正常的前列腺。结论 总之，据我们所知，该研究代表了人类 PCa 组织标本中单个蛋白质复合物的第一次大规模和定量的（尽管是间接的）比较。它可以作为一个有用的资源来更好地了解原发性 PCa 中蛋白质复合物的失调。与正常前列腺相比，高级PCa中线粒体复合物I的四个亚复合物显着增加。结论 总之，据我们所知，该研究代表了人类 PCa 组织标本中单个蛋白质复合物的第一次大规模和定量的（尽管是间接的）比较。它可以作为一个有用的资源来更好地了解原发性 PCa 中蛋白质复合物的失调。与正常前列腺相比，高级PCa中线粒体复合物I的四个亚复合物显着增加。结论 总之，据我们所知，该研究代表了人类 PCa 组织标本中单个蛋白质复合物的第一次大规模和定量的（尽管是间接的）比较。它可以作为一个有用的资源来更好地了解原发性 PCa 中蛋白质复合物的失调。