Differential expression between African-ancestry and White patients diagnosed with Triple-Negative Breast Cancer: EGFR, Myc, Bcl2 and β-Catenin as ancestry-associated markers

作者: Ana T. Matias , Ana Jacinta-Fernandes , Ana-Teresa Maia , Sofia Braga , António Jacinto

DOI: 10.1101/2020.11.13.381608

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摘要: PurposeTriple-negative breast cancer (TNBC) has a higher incidence, younger age of onset, and more aggressive behavior in African-ancestry women. Biological disparities have been suggested as an important factor influencing the ancestry-associated TNBC discrepancy. In this study, we sought to identify differential gene protein expression between White patients, controlling for patients menopause status pathological staging at diagnosis. MethodsDifferential analyses (DGEA) were performed using RNA-sequencing data from The Cancer Genome Atlas (TCGA). Gene set enrichment analysis (GSEA) Ingenuity Pathway Analysis (IPA), with focus on network design, highlight candidate genes further validation through immunohistochemistry samples followed Portugal. ResultsWith 52 African-American 90 included, TCGAs corroborate that incidence (28.42% vs 11.89%, p<0.0001). Particularly, premenopausal stage II disease also significantly lower survival probability, comparing (log-rank p=0.019 0.0038, respectively). DGEA results suggest profile differences are associated than status. Hippo pathway cellular community sets downregulated, while is upregulated African-Americans, patients. Furthermore, MAPK when disease. Due their central role highly scored networks resulted IPAs EGFR, Myc Bcl2 selected immunohistochemistry. We included {beta}-Catenin study it consensually reported be required tumorigenesis. Although used experiments geographically culturally distinct, both groups mostly western-African ancestry and, interesting, matched. ConclusionsWe found patterns TNBCs, particularly or staging. Myc, {beta}-catenin matching distinct populations these markers being indicators TNBCs development.

参考文章(109)
Lisa A. Levin, Guillermo F. Mendoza, Benjamin M. Grupe, Jennifer P. Gonzalez, Brittany Jellison, Greg Rouse, Andrew R. Thurber, Anders Waren, Biodiversity on the Rocks: Macrofauna Inhabiting Authigenic Carbonate at Costa Rica Methane Seeps. PLOS ONE. ,vol. 10, ,(2015) , 10.1371/JOURNAL.PONE.0131080
Nakopoulou, Gakiopoulou, Keramopoulos, Giannopoulou, Athanassiadou, Mavrommatis, Davaris, c‐met tyrosine kinase receptor expression is associated with abnormal β‐catenin expression and favourable prognostic factors in invasive breast carcinoma Histopathology. ,vol. 36, pp. 313- 325 ,(2000) , 10.1046/J.1365-2559.2000.00847.X
Patricia Marti, Claudia Stein, Tanja Blumer, Yann Abraham, Michael T. Dill, Monika Pikiolek, Vanessa Orsini, Giorgia Jurisic, Philippe Megel, Zuzanna Makowska, Claudia Agarinis, Luigi Tornillo, Tewis Bouwmeester, Heinz Ruffner, Andreas Bauer, Christian N. Parker, Tobias Schmelzle, Luigi M. Terracciano, Markus H. Heim, Jan S. Tchorz, YAP promotes proliferation, chemoresistance, and angiogenesis in human cholangiocarcinoma through TEAD transcription factors Hepatology. ,vol. 62, pp. 1497- 1510 ,(2015) , 10.1002/HEP.27992
Tanya Keenan, Beverly Moy, Edmund A. Mroz, Kenneth Ross, Andrzej Niemierko, James W. Rocco, Steven Isakoff, Leif W. Ellisen, Aditya Bardia, Comparison of the Genomic Landscape Between Primary Breast Cancer in African American Versus White Women and the Association of Racial Differences With Tumor Recurrence Journal of Clinical Oncology. ,vol. 33, pp. 3621- 3627 ,(2015) , 10.1200/JCO.2015.62.2126
Deborah A. Dillon, Tom D'Aquila, David L. Rimm, Eric R. Fearon, Albert B. Reynolds, The expression of p120ctn protein in breast cancer is independent of alpha- and beta-catenin and E-cadherin. American Journal of Pathology. ,vol. 152, pp. 75- 82 ,(1998)
Karin Collett, Ingunn M Stefansson, Johan Eide, Audun Braaten, Hege Wang, Geir Egil Eide, Steinar Ø Thoresen, William D Foulkes, Lars A Akslen, A Basal Epithelial Phenotype Is More Frequent in Interval Breast Cancers Compared with Screen Detected Tumors Cancer Epidemiology Biomarkers & Prevention. ,vol. 14, pp. 1108- 1112 ,(2005) , 10.1158/1055-9965.EPI-04-0394
Dezheng Huo, Francis Ikpatt, Andrey Khramtsov, Jean-Marie Dangou, Rita Nanda, James Dignam, Bifeng Zhang, Tatyana Grushko, Chunling Zhang, Olayiwola Oluwasola, David Malaka, Sani Malami, Abayomi Odetunde, Adewumi O. Adeoye, Festus Iyare, Adeyinka Falusi, Charles M. Perou, Olufunmilayo I. Olopade, Population Differences in Breast Cancer: Survey in Indigenous African Women Reveals Over-Representation of Triple-Negative Breast Cancer Journal of Clinical Oncology. ,vol. 27, pp. 4515- 4521 ,(2009) , 10.1200/JCO.2008.19.6873
L. Vona-Davis, D. P. Rose, H. Hazard, M. Howard-McNatt, F. Adkins, J. Partin, G. Hobbs, Triple-Negative Breast Cancer and Obesity in a Rural Appalachian Population Cancer Epidemiology, Biomarkers & Prevention. ,vol. 17, pp. 3319- 3324 ,(2008) , 10.1158/1055-9965.EPI-08-0544
Michael K. Wendt, Whitney K. Williams, Pete E. Pascuzzi, Nikolas G. Balanis, Barbara J. Schiemann, Cathleen R. Carlin, William P. Schiemann, The Antitumorigenic Function of EGFR in Metastatic Breast Cancer is Regulated by Expression of Mig6 Neoplasia. ,vol. 17, pp. 124- 133 ,(2015) , 10.1016/J.NEO.2014.11.009