TY - JOUR
T1 - Comparative analysis of triple-negative breast cancer transcriptomics of Kenyan, African American and Caucasian Women
AU - Saleh, Mansoor
AU - Chandrashekar, Darshan Shimoga
AU - Shahin, Sayed
AU - Agarwal, Sumit
AU - Kim, Hyung Gyoon
AU - Behring, Michael
AU - Shaikh, Asim Jamal
AU - Moloo, Zahir
AU - Eltoum, Isam Eldin A.
AU - Yates, Clayton
AU - Varambally, Sooryanarayana
AU - Manne, Upender
N1 - Publisher Copyright:
© 2021
PY - 2021/7
Y1 - 2021/7
N2 - Purpose: : Triple-negative breast cancer (TNBC) patients of various ethnic groups often have discrete clinical presentations and outcomes. Women of African descent have a disproportionately higher chance of developing TNBCs. The aim of the current study was to establish the transcriptome of TNBCs from Kenyan (KE) women of Bantu origin and compare it to those TNBCs of African-Americans (AA) and Caucasians (CA) for identifying KE TNBC-specific molecular determinants of cancer progression and potential biomarkers of clinical outcomes. Patients and Methods: : Pathology-confirmed TNBC tissues from Kenyan women of Bantu origin (n = 15) and age and stage range matched AA (n = 19) and CA (n = 23) TNBCs of patients from Alabama were included in this study. RNA was isolated from paraffin-embedded tissues, and expression was analyzed by RNA sequencing. Results: : At clinical presentation, young KE TNBC patients have tumors of higher stages. Differential expression analysis identified 160 up-regulated and 178 down-regulated genes in KE TNBCs compared to AA and CA TNBCs. Validation analyses of the TCGA breast cancer data identified 45 KE TNBC-specific genes that are involved in the apoptosis (ACTC1, ERCC6 and CD14), cell proliferation (UHRF2, KDM4C, UHMK1, KCNH5, KRT18, CSF1R and S100A13), and Wnt signaling (BCL9L) pathways. Conclusions: : In this study, we identified biomarkers that are specific for KE TNBC patients of Bantu origin. Further study with a larger sample size of matched tumors could confirm our findings. If biologically confirmed, these molecular determinants could have clinical and biological implications and serve as targets for development of personalized therapeutics for KE TNBC patients.
AB - Purpose: : Triple-negative breast cancer (TNBC) patients of various ethnic groups often have discrete clinical presentations and outcomes. Women of African descent have a disproportionately higher chance of developing TNBCs. The aim of the current study was to establish the transcriptome of TNBCs from Kenyan (KE) women of Bantu origin and compare it to those TNBCs of African-Americans (AA) and Caucasians (CA) for identifying KE TNBC-specific molecular determinants of cancer progression and potential biomarkers of clinical outcomes. Patients and Methods: : Pathology-confirmed TNBC tissues from Kenyan women of Bantu origin (n = 15) and age and stage range matched AA (n = 19) and CA (n = 23) TNBCs of patients from Alabama were included in this study. RNA was isolated from paraffin-embedded tissues, and expression was analyzed by RNA sequencing. Results: : At clinical presentation, young KE TNBC patients have tumors of higher stages. Differential expression analysis identified 160 up-regulated and 178 down-regulated genes in KE TNBCs compared to AA and CA TNBCs. Validation analyses of the TCGA breast cancer data identified 45 KE TNBC-specific genes that are involved in the apoptosis (ACTC1, ERCC6 and CD14), cell proliferation (UHRF2, KDM4C, UHMK1, KCNH5, KRT18, CSF1R and S100A13), and Wnt signaling (BCL9L) pathways. Conclusions: : In this study, we identified biomarkers that are specific for KE TNBC patients of Bantu origin. Further study with a larger sample size of matched tumors could confirm our findings. If biologically confirmed, these molecular determinants could have clinical and biological implications and serve as targets for development of personalized therapeutics for KE TNBC patients.
UR - http://www.scopus.com/inward/record.url?scp=85103703316&partnerID=8YFLogxK
U2 - 10.1016/j.tranon.2021.101086
DO - 10.1016/j.tranon.2021.101086
M3 - Article
AN - SCOPUS:85103703316
SN - 1936-5233
VL - 14
JO - Translational Oncology
JF - Translational Oncology
IS - 7
M1 - 101086
ER -
