Multiethnic PDX models predict a possible immune signature associated with TNBC of African ancestry.

Autor: Jiagge EM; Henry Ford Cancer Institute/Henry Ford Health System, 2799 W Grand Blvd, Detroit, MI, 48202, USA. ejiagge1@hfhs.org.; Department of Internal Medicine, Michigan Medicine, University of Michigan, 1500 East Medical Center Drive, RCC 7314, Ann Arbor, MI, 48105, USA. ejiagge1@hfhs.org.; Rogel Cancer Center, University of Michigan, Ann Arbor, MI, 48105, USA. ejiagge1@hfhs.org., Ulintz PJ; Department of Internal Medicine, Michigan Medicine, University of Michigan, 1500 East Medical Center Drive, RCC 7314, Ann Arbor, MI, 48105, USA.; Rogel Cancer Center, University of Michigan, Ann Arbor, MI, 48105, USA., Wong S; The Translational Genomics Research Institute, Phoenix, AZ, USA., McDermott SP; Department of Internal Medicine, Michigan Medicine, University of Michigan, 1500 East Medical Center Drive, RCC 7314, Ann Arbor, MI, 48105, USA., Fossi SI; Henry Ford Cancer Institute/Henry Ford Health System, 2799 W Grand Blvd, Detroit, MI, 48202, USA.; Department of Internal Medicine, Michigan Medicine, University of Michigan, 1500 East Medical Center Drive, RCC 7314, Ann Arbor, MI, 48105, USA., Suhan TK; Rogel Cancer Center, University of Michigan, Ann Arbor, MI, 48105, USA.; Department of Urology, Michigan Medicine, University of Michigan, Ann Arbor, USA., Hoenerhoff MJ; Unit for Laboratory Animal Medicine, University of Michigan, Ann Arbor, USA., Bensenhaver JM; Henry Ford Cancer Institute/Henry Ford Health System, 2799 W Grand Blvd, Detroit, MI, 48202, USA., Salem B; Michigan Institute for Clinical & Health Research, Ann Arbor, USA., Dziubinski M; Rogel Cancer Center, University of Michigan, Ann Arbor, MI, 48105, USA., Oppong JK; Komfo Anokye Teaching Hospital, Kumasi, Ghana., Aitpillah F; Komfo Anokye Teaching Hospital, Kumasi, Ghana., Ishmael K; Komfo Anokye Teaching Hospital, Kumasi, Ghana., Osei-Bonsu E; Komfo Anokye Teaching Hospital, Kumasi, Ghana., Adjei E; Komfo Anokye Teaching Hospital, Kumasi, Ghana., Baffour A; Komfo Anokye Teaching Hospital, Kumasi, Ghana., Aldrich J; The Translational Genomics Research Institute, Phoenix, AZ, USA., Kurdoglu A; The Translational Genomics Research Institute, Phoenix, AZ, USA., Fernando K; Henry Ford Cancer Institute/Henry Ford Health System, 2799 W Grand Blvd, Detroit, MI, 48202, USA., Craig DW; Keck School of Medicine, University of Southern California, Los Angeles, CA, USA., Trent JM; The Translational Genomics Research Institute, Phoenix, AZ, USA., Li J; Rogel Cancer Center, University of Michigan, Ann Arbor, MI, 48105, USA., Chitale D; Henry Ford Cancer Institute/Henry Ford Health System, 2799 W Grand Blvd, Detroit, MI, 48202, USA., Newman LA; New York-Presbyterian/Weill Cornell Medical Center and Weill Cornell Medicine, New York, NY, USA., Carpten JD; Keck School of Medicine, University of Southern California, Los Angeles, CA, USA., Wicha MS; Department of Internal Medicine, Michigan Medicine, University of Michigan, 1500 East Medical Center Drive, RCC 7314, Ann Arbor, MI, 48105, USA.; Rogel Cancer Center, University of Michigan, Ann Arbor, MI, 48105, USA., Merajver SD; Department of Internal Medicine, Michigan Medicine, University of Michigan, 1500 East Medical Center Drive, RCC 7314, Ann Arbor, MI, 48105, USA. smerajve@med.umich.edu.; Rogel Cancer Center, University of Michigan, Ann Arbor, MI, 48105, USA. smerajve@med.umich.edu.
Jazyk: angličtina
Zdroj: Breast cancer research and treatment [Breast Cancer Res Treat] 2021 Apr; Vol. 186 (2), pp. 391-401. Date of Electronic Publication: 2021 Feb 12.
DOI: 10.1007/s10549-021-06097-8
Abstrakt: Purpose: Triple-negative breast cancer (TNBC) is an aggressive subtype most prevalent among women of Western Sub-Saharan African ancestry. It accounts for 15-25% of African American (AA) breast cancers (BC) and up to 80% of Ghanaian breast cancers, thus contributing to outcome disparities in BC for black women. The aggressive biology of TNBC has been shown to be regulated partially by breast cancer stem cells (BCSC) which mediate tumor recurrence and metastasis and are more abundant in African breast tumors.
Methods: We studied the biological differences between TNBC in women with African ancestry and those of Caucasian women by comparing the gene expression of the BCSC. From low-passage patient derived xenografts (PDX) from Ghanaian (GH), AA, and Caucasian American (CA) TNBCs, we sorted for and sequenced the stem cell populations and analyzed for differential gene enrichment.
Results: In our cohort of TNBC tumors, we observed that the ALDH expressing stem cells display distinct ethnic specific gene expression patterns, with the largest difference existing between the GH and AA ALDH+ cells. Furthermore, the tumors from the women of African ancestry [GH/AA] had ALDH stem cell (SC) enrichment for expression of immune related genes and processes. Among the significantly upregulated genes were CD274 (PD-L1), CXCR9, CXCR10 and IFI27, which could serve as potential drug targets.
Conclusions: Further exploration of the role of immune regulated genes and biological processes in BCSC may offer insight into developing novel approaches to treating TNBC to help ameliorate survival disparities in women with African ancestry.
Databáze: MEDLINE
Externí odkaz: