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首页> 外文期刊>Molecular & cellular proteomics: MCP >Immunoseroproteomic Profiling in African American Men with Prostate Cancer: Evidence for an Autoantibody Response to Glycolysis and Plasminogen-Associated Proteins
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Immunoseroproteomic Profiling in African American Men with Prostate Cancer: Evidence for an Autoantibody Response to Glycolysis and Plasminogen-Associated Proteins

机译：非洲裔美国男性前列腺癌的免疫人体工程学分析：糖酵解和纤溶酶原相关蛋白自身抗体反应的证据。

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African American (AA) men suffer from a disproportionately high incidence and mortality of prostate cancer (PCa) compared with other racial/ethnic groups. Despite these disparities, African American men are underrepresented in clinical trials and in studies on PCa biology and biomarker discovery. We used immunoseroproteomics to profile antitumor autoantibody responses in AA and European American (EA) men with PCa, and explored differences in these responses. This minimally invasive approach detects autoantibodies to tumor-associated antigens that could serve as clinical biomarkers and immunotherapeutic agents. Sera from AA and EA men with PCa were probed by immunoblotting against PC3 cell proteins, with AA sera showing stronger immunoreactivity. Mass spectrometry analysis of immunoreactive protein spots revealed that several AA sera contained autoantibodies to a number of proteins associated with both the glycolysis and plasminogen pathways, particularly to alpha-enolase (ENO1). The proteomic data is deposited in ProteomeXchange with identifier PXD003968. Analysis of sera from 340 racially diverse men by enzyme-linked immunosorbent assays (ELISA) showed higher frequency of anti-ENO1 autoantibodies in PCa sera compared with control sera. We observed differences between AA-PCa and EA-PCa patients in their immunoreactivity against ENO1. Although EA-PCa sera reacted with higher frequency against purified ENO1 in ELISA and recognized by immunoblotting the endogenous cellular ENO1 across a panel of prostate cell lines, AA-PCa sera reacted weakly against this protein by ELISA but recognized it by immunoblotting preferentially in metastatic cell lines. These race-related differences in immunoreactivity to ENO1 could not be accounted by differential autoantibody recognition of phosphoepitopes within this antigen. Proteomic analysis revealed differences in the posttranslational modification profiles of ENO1 variants differentially recognized by AA-PCa and EA-PCa sera. These intriguing results suggest the possibility of race-related differences in the antitumor autoantibody response in PCa, and have implications for defining novel biological determinants of PCa health disparities.
机译：与其他种族/族裔群体相比，非裔美国人（AA）男性罹患前列腺癌（PCa）的比例高，死亡率高。尽管存在这些差异，但在PCa生物学和生物标志物发现的临床试验以及研究中，非洲裔美国人的人数仍不足。我们使用免疫血清蛋白质组学来分析AA和欧美人（EA）PCa患者的抗肿瘤自身抗体反应，并探讨这些反应的差异。这种微创方法可以检测与肿瘤相关抗原的自身抗体，这些抗体可以用作临床生物标志物和免疫治疗剂。通过针对PC3细胞蛋白的免疫印迹对来自AA和EA患有PCa的男性的血清进行了探测，其中AA血清显示出更强的免疫反应性。免疫反应蛋白斑点的质谱分析表明，一些AA血清含有针对与糖酵解和纤溶酶原途径（特别是与α-烯醇酶（ENO1））相关的许多蛋白质的自身抗体。蛋白质组学数据以标识符PXD003968存放在ProteomeXchange中。通过酶联免疫吸附测定（ELISA）对340名不同种族男子的血清进行的分析显示，与对照血清相比，PCa血清中抗ENO1自身抗体的频率更高。我们观察到AA-PCa和EA-PCa患者对ENO1的免疫反应性存在差异。尽管EA-PCa血清在ELISA中对纯化的ENO1的反应频率更高，并且通过一系列前列腺细胞系对内源性细胞ENO1的免疫印迹而被识别，但是AA-PCa血清通过ELISA对这种蛋白质的反应较弱，但在转移细胞中优先通过免疫印迹识别线。这些与种族相关的对ENO1免疫反应性的差异无法通过该抗原内磷酸表位的差异自身抗体识别来解释。蛋白质组学分析显示，AA-PCa和EA-PCa血清识别的ENO1变异的翻译后修饰谱存在差异。这些有趣的结果表明，在PCa中抗肿瘤自身抗体反应中种族相关差异的可能性，对于定义PCa健康差异的新生物学决定因素具有影响。

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