Torres-Luquis Odalys, Madden Krystal, N'dri N'sanh Mr, Berg Richard, Olopade Olufunmilayo F, Ngwa Wilfred, Abuidris Dafalla, Mittal Suresh, Lyn-Cook Beverly, Mohammed Sulma I
Department of Comparative Pathobiology, Purdue University, West Lafayette, IN, USA,
Purdue University Center for Cancer Research, Purdue University, West Lafayette, IN, USA,
Breast Cancer (Dove Med Press). 2018 Dec 20;11:1-12. doi: 10.2147/BCTT.S185960. eCollection 2019.
Triple-negative breast cancer (TNBC) is more prevalent in African and African American (AA) women compared to European American (EA) women. African and AA women diagnosed with TNBC experience high frequencies of metastases and less favorable outcomes. Emerging evidence indicates that this disparity may in fact be the result of the uniquely aggressive biology of African and AA disease.
To understand the reasons for TNBC in AA aggressive biology, we designed the present study to examine the proteomic profiles of TNBC and luminal A (LA) breast cancer within and across patients' racial demographic groups in order to identify proteins or molecular pathways altered in TNBC that offer some explanation for its aggressiveness and potential targets for treatment.
Proteomic profiles of TNBC, LA tumors, and their adjacent normal tissues from AA and EA women were obtained using 2-dimensional gel electrophoresis and bioinformatics, and differentially expressed proteins were validated by Western blot and immunohistochemistry. Our data showed that a number of proteins have significantly altered in expression in LA tumors compared to TNBC, both within and across patients' racial demographic groups. The differentially overexpressed proteins in TNBC (compared to LA) of AA samples were distinct from those in TNBC (compared to LA) of EA women samples. Among the signaling pathways altered in AA TNBC compared to EA TNBC are innate immune signaling, calpain protease, and pyrimidine de novo synthesis pathways. Furthermore, liver LXR/RXR signaling pathway was altered between LA and TNBC in AA women and may be due to the deficiency of the CYP7B1 enzyme responsible for cholesterol degradation.
These findings suggest that TNBC in AA women enriched in signaling pathways that are different from TNBC in EA women. Our study draws a link between LXR/RXR expression, cholesterol, obesity, and the TNBC in AA women.
与欧美女性相比，三阴性乳腺癌（TNBC）在非洲及非裔美国（AA）女性中更为普遍。被诊断为TNBC的非洲及AA女性发生转移的频率较高，预后较差。新出现的证据表明，这种差异可能实际上是非洲及AA女性疾病独特的侵袭性生物学特性导致的结果。
为了解AA女性TNBC侵袭性生物学特性的原因，我们设计了本研究，以检查TNBC和管腔A型（LA）乳腺癌在患者种族人口统计学组内和组间的蛋白质组学概况，以便识别TNBC中发生改变的蛋白质或分子途径，这些改变可为其侵袭性提供一些解释，并作为潜在的治疗靶点。
使用二维凝胶电泳和生物信息学获得AA和EA女性的TNBC、LA肿瘤及其相邻正常组织的蛋白质组学概况，并通过蛋白质印迹和免疫组织化学对差异表达的蛋白质进行验证。我们的数据表明，与TNBC相比，许多蛋白质在LA肿瘤中的表达在患者种族人口统计学组内和组间均有显著改变。AA样本的TNBC（与LA相比）中差异过表达的蛋白质与EA女性样本的TNBC（与LA相比）中的不同。与EA TNBC相比，AA TNBC中改变的信号通路包括天然免疫信号通路、钙蛋白酶和嘧啶从头合成途径。此外，AA女性的LA和TNBC之间肝脏LXR/RXR信号通路发生改变，这可能是由于负责胆固醇降解的CYP7B1酶缺乏所致。
这些发现表明，AA女性的TNBC富含与EA女性TNBC不同的信号通路。我们的研究揭示了LXR/RXR表达、胆固醇、肥胖与AA女性TNBC之间的联系。
