Srivastava Meera, Eidelman Ofer, Craig James, Starr Joshua, Kvecher Leonid, Liu Jianfang, Hueman Matthew, Pollard Harvey B, Hu Hai, Shriver Craig D
Department of Anatomy, Physiology and Genetics, and Collaborative Health Initiative Research Program, Uniformed Services University Health Sciences, 4301 Jones Bridge Road, Bethesda, MD.
Chan Soon-Shiong Institute of Molecular Medicine, 620 7th St, Windber, PA.
Mil Med. 2019 Mar 1;184(Suppl 1):652-657. doi: 10.1093/milmed/usy417.
African American (AA) women are often diagnosed with more aggressive breast cancers and have worse survival outcomes than their Caucasian American (CA) counterparts. However, a comprehensive understanding of this disparity remains unclear. In this study, we attempted to identify the race-specific non-invasive protein biomarkers that may particularly benefit interventions aimed at reducing the risk of recurrence and metastasis in breast cancers (BrCa). Our technical strategy has been to discover candidate protein biomarkers in patient sera using a high throughput antibody microarray platform. A total of 240 subjects were selected, composed of controls and all immunohistochemistry-based subtypes of breast cancer cases, subdivided by pre- and post-menopausal status and by race. A global Wilcoxon analysis comparing no-cancer controls and cancer patients identified Pyk2, SAPK/JNK, and phosphatase and tensin homolog as present in higher concentrations in cancer patient serum. A paired t-test revealed that c-kit and Rb are significantly over-represented in AA cancer serum when compared to CA cancer serum. Interestingly, VEGFR2, a protein linked to BrCa metastasis and poor prognosis, was significantly over-represented in AA cancer serum compared to AA controls; however, this was not found in CA cancer serum compared to CA controls, suggesting a possible explanation for the higher incidence of aggressive BrCa in AA versus CA patients. Through examining race-specific differences in the protein landscape of BrCa patient serum, the identified proteins could lay the groundwork for the development of an all-inclusive "liquid mammogram test."
非裔美国(AA)女性往往被诊断出患有侵袭性更强的乳腺癌,其生存结果比美国白人(CA)女性更差。然而,对这种差异的全面理解仍不明确。在本研究中,我们试图确定种族特异性的非侵入性蛋白质生物标志物,这些标志物可能特别有助于旨在降低乳腺癌(BrCa)复发和转移风险的干预措施。我们的技术策略是使用高通量抗体微阵列平台在患者血清中发现候选蛋白质生物标志物。总共选择了240名受试者,包括对照组以及所有基于免疫组织化学的乳腺癌病例亚型,并按绝经前后状态和种族进行细分。一项比较无癌对照组和癌症患者的全局Wilcoxon分析确定,粘着斑激酶2(Pyk2)、应激活化蛋白激酶/氨基末端激酶(SAPK/JNK)以及张力蛋白同源磷酸酶在癌症患者血清中的浓度更高。配对t检验显示,与CA癌症血清相比,c-kit和视网膜母细胞瘤蛋白(Rb)在AA癌症血清中的含量显著过高。有趣的是,与AA对照组相比,与BrCa转移和预后不良相关的蛋白血管内皮生长因子受体2(VEGFR2)在AA癌症血清中的含量显著过高;然而,与CA对照组相比,在CA癌症血清中未发现这种情况,这可能解释了AA患者中侵袭性BrCa发病率高于CA患者的原因。通过检查BrCa患者血清蛋白质图谱中的种族特异性差异,所确定的蛋白质可为开发一种全面的“液体乳房X线检测”奠定基础。