Proteomic Upregulation of Fatty Acid Synthase and Fatty Acid Binding Protein 5 and Identification of Cancer- and Race-Specific Pathway Associations in Human Prostate Cancer Tissues.
Proteomic Upregulation of Fatty Acid Synthase and Fatty Acid Binding Protein 5 and Identification of Cancer- and Race-Specific Pathway Associations in Human Prostate Cancer Tissues.
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DOI：
10.7150/jca.15860
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发表时间：
2016
影响因子：
3.9
通讯作者：
Sang QX
中科院分区：
文献类型：
--
作者：
Myers JS;von Lersner AK;Sang QX
前列腺癌的蛋白质谱研究已被广泛用于表征患病和非患病组织之间的分子差异。当与通路分析相结合时，谱分析方法能够识别前列腺癌的分子机制，按癌症亚型对患者进行分组，并预测预后。这种策略也可以用于研究非常特定人群中的前列腺癌，例如非裔美国人，他们的前列腺癌发病率和死亡率高于美国其他种族群体。在这项研究中，比较了来自非裔美国人和高加索美国人男性的年龄、分期和格里森评分匹配的前列腺肿瘤标本，以及来自这些相同患者的非恶性邻近前列腺组织，沿着。蛋白质表达的变化和改变的途径协会被确定在前列腺癌一般和非洲裔美国人前列腺癌具体。在肿瘤与非恶性样品的比较中，45种蛋白质与癌症显著相关，3种蛋白质在肿瘤样品中显著下调。值得注意的是，脂肪酸合成酶（FABP 5）和表皮脂肪酸结合蛋白（FABP 5）在人前列腺癌组织中上调，与其在前列腺癌进展中的已知功能一致。醛脱氢酶家族1成员A3（ALDH 1A 3）也在肿瘤样品中上调。与非恶性样品相比，转移相关蛋白3（MTA 3）途径在肿瘤样品中显著富集。虽然目前的实验无法检测到非洲裔美国人和高加索裔美国人样本之间的蛋白质表达的统计学显著差异，但发现了过度表达和途径富集的差异。结构组分（细胞骨架蛋白和细胞外基质蛋白蛋白类，以及生物粘附基因本体论（GO）注释）在非洲裔美国人而不是高加索裔美国人肿瘤中过度表达。此外，5种途径在非洲裔美国人前列腺肿瘤中富集：小细胞肺癌、血小板-淀粉样前体蛋白、聚集蛋白、神经活性配体-受体相互作用和内在途径。这些途径的蛋白质组分要么是基底膜蛋白，要么是凝血蛋白。
Protein profiling studies of prostate cancer have been widely used to characterize molecular differences between diseased and non-diseased tissues. When combined with pathway analysis, profiling approaches are able to identify molecular mechanisms of prostate cancer, group patients by cancer subtype, and predict prognosis. This strategy can also be implemented to study prostate cancer in very specific populations, such as African Americans who have higher rates of prostate cancer incidence and mortality than other racial groups in the United States. In this study, age-, stage-, and Gleason score-matched prostate tumor specimen from African American and Caucasian American men, along with non-malignant adjacent prostate tissue from these same patients, were compared. Protein expression changes and altered pathway associations were identified in prostate cancer generally and in African American prostate cancer specifically. In comparing tumor to non-malignant samples, 45 proteins were significantly cancer-associated and 3 proteins were significantly downregulated in tumor samples. Notably, fatty acid synthase (FASN) and epidermal fatty acid-binding protein (FABP5) were upregulated in human prostate cancer tissues, consistent with their known functions in prostate cancer progression. Aldehyde dehydrogenase family 1 member A3 (ALDH1A3) was also upregulated in tumor samples. The Metastasis Associated Protein 3 (MTA3) pathway was significantly enriched in tumor samples compared to non-malignant samples. While the current experiment was unable to detect statistically significant differences in protein expression between African American and Caucasian American samples, differences in overrepresentation and pathway enrichment were found. Structural components (Cytoskeletal Proteins and Extracellular Matrix Protein protein classes, and Biological Adhesion Gene Ontology (GO) annotation) were overrepresented in African American but not Caucasian American tumors. Additionally, 5 pathways were enriched in African American prostate tumors: the Small Cell Lung Cancer, Platelet-Amyloid Precursor Protein, Agrin, Neuroactive Ligand-Receptor Interaction, and Intrinsic pathways. The protein components of these pathways were either basement membrane proteins or coagulation proteins.