Abstract
Despite recent advances, breast cancer (BrCa) still affects many women and the impact is disproportional in African Americans (AA) compared to European Americans (EA). Addressing socioeconomic and behavioral status has not been enough to reduce disparity, suggesting contribution of biological differences in BrCa disparity. Our laboratory was first to show involvement of CC chemokines in BrCa. In this study, using ONCOMINE, TCGA, bc-GenExMiner and KMplotter, we examined the association of CC chemokines in BrCa outcomes and disparity. We show over-expression of CCL5, -7, -11, -17, -20, -22 and -25 in BrCa tissues. High mRNA levels of CCL7, -8, -17, -20 and -25 predicted a decrease in overall survival (OS). CCL7 and CCL8 were associated with decreased relapse-free survival. Expression of CCL17 and CCL25 was associated with decreased OS in AA. In EA, CCL8 was associated with decreased OS. Expression of CCL5, -7, -8, -17, -20 and -25 was highest in TNBC. Expression of CCL11 and CCL22 was associated with HER2. CCL7, -8, -17, -20 and -25 were elevated in AAs. In conclusion, our analysis suggests significant association of CC-chemokines in BrCa progression, OS and disparate disease outcome in AA compared to EA patients.
Highlights
Breast cancer (BrCa) alone accounts for 30% of all new cancers diagnosed in women[1] and is the second leading cause of cancer related deaths in women after lung cancer[1]
Using the ONCOMINE database (TCGA breast invasive carcinoma dataset), out of all known CC chemokines 7 CC chemokines’ [(CCL5 (FC = 1.6, p = 8.6e−05), CCL7 (FC = 4.5, p = 1.43e−14), CCL11 (FC = 5.5, p = 1.29e−31), CCL17 (FC = 2.0, p = 3.32e−09), CCL20 (FC = 2.2, p = 2.07e−06), CCL22 (FC = 1.44, p = 1.5e−04) and CCL25 (FC = 1.6, p = 1.33e−08)] mRNA were significantly elevated in breast cancer (BrCa) compared to normal tissues (Table 1)
Chemokine receptors CCR1 and CCR5 are expressed on monocytes and facilitate their recruitment under chemotactic gradient of CCL5 and CCL731 and play a crucial role in tumor progression
Summary
Breast cancer (BrCa) alone accounts for 30% of all new cancers diagnosed in women[1] and is the second leading cause of cancer related deaths in women after lung cancer[1]. Among all BrCa types Triple Negative Breast Cancer (TNBC), which lacks estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) is the most lethal type This subtype is further elucidated into 6 subtypes identified by cluster analysis[3]. Chemokines are a large family of small cytokines, which are classified into 4 different subgroups (C, CC, CXC and CX3C), based on cysteine residues These molecules are responsible for immune cell trafficking and shaping the immune system. In this study we have utilized large-scale bioinformatics to ascertain CC chemokine expression in BrCa patients based on clinical parameters, respective prognosis and have presented evidence suggesting association of CC chemokines with BrCa progression, TNBC and racial disparity in overall survival (OS)
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