Protein signatures to distinguish aggressive from indolent prostate cancer.
Protein signatures to distinguish aggressive from indolent prostate cancer.
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DOI：
10.1002/pros.24307
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发表时间：
2022-04
期刊：
影响因子：
--
通讯作者：
Pitteri SJ
中科院分区：
文献类型：
--
作者：
Garcia-Marques F;Liu S;Totten SM;Bermudez A;Tanimoto C;Hsu EC;Nolley R;Hembree A;Stoyanova T;Brooks JD;Pitteri SJ
区分男性侵袭性前列腺癌和惰性前列腺癌对临床局限性前列腺癌的治疗至关重要。侵袭性疾病的分子特征可以帮助男性克服这一重大临床挑战，减少不必要的治疗，并允许更适当的治疗侵袭性疾病。我们对22名接受前列腺癌手术的男性的正常和恶性前列腺组织进行了基于质谱的蛋白质组学分析。前列腺癌样本包括等级组（3至5），其中8名患者出现复发，14名患者无复发证据，平均随访时间为6.8年。为了更好地了解前列腺癌侵袭性的生物学途径，我们进行了系统生物学分析和基因富集分析。选择区分复发性和非复发性癌症的蛋白质，通过对含有来自复发性和非复发性前列腺癌患者的较大队列的样品的组织微阵列进行免疫组织化学分析进行验证。鉴定了对应于3，313种不同蛋白质的24，037种独特肽（错误发现率< 1%），其绝对丰度范围跨越7个数量级。在这些蛋白质中，115种蛋白质在复发性与非复发性癌症的组织中显示出显著（P < 0.01）不同的水平。对复发和非复发病例中所有差异表达蛋白的分析鉴定了几种蛋白质网络，其中最显著的一种是网络中约24%的蛋白质受YY 1转录因子调节（校正P < 0.001）。在组织微阵列上，三种差异表达的蛋白质，POR4，CALR和CTSD的强免疫组织化学染色水平验证了它们与较短的患者生存期的相关性。所鉴定的蛋白质特征可以提高对侵袭性前列腺癌分子驱动因素的理解，并可用作候选预后生物标志物。
Distinguishing men with aggressive from indolent prostate cancer is critical to decisions in the management of clinically localized prostate cancer. Molecular signatures of aggressive disease could help men overcome this major clinical challenge by reducing unnecessary treatment and allowing more appropriate treatment of aggressive disease. We performed a mass spectrometry-based proteomic analysis of normal and malignant prostate tissues from 22 men who underwent surgery for prostate cancer. Prostate cancer samples included Grade Groups (3 to 5), with 8 patients experiencing recurrence and 14 without evidence of recurrence with a mean of 6.8 years of follow-up. To better understand the biological pathways underlying prostate cancer aggressiveness, we performed a systems biology analysis and gene enrichment analysis. Proteins that distinguished recurrent from non-recurrent cancer were chosen for validation by immunohistochemical analysis on tissue microarrays containing samples from a larger cohort of patients with recurrent and non-recurrent prostate cancer. 24,037 unique peptides (false discovery rate < 1%) corresponding to 3,313 distinct proteins were identified with absolute abundance ranges spanning seven orders of magnitude. Of these proteins, 115 showed significantly (P < 0.01) different levels in tissues from recurrent versus non-recurrent cancers. Analysis of all differentially expressed proteins in recurrent and non-recurrent cases identified several protein networks, most prominently one in which approximately 24% of the proteins in the network were regulated by the YY1 transcription factor (adjusted P < 0.001). Strong immunohistochemical staining levels of three differentially expressed proteins, POSTN, CALR, and CTSD, on a tissue microarray validated their association with shorter patient survival. The protein signatures identified could improve understanding of the molecular drivers of aggressive prostate cancer and be used as candidate prognostic biomarkers.
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影响因子：
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作者：
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影响因子：
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作者：
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DOI：
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发表时间：
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期刊：
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作者：
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