Kaiso is highly expressed in TNBC tissues of women of African ancestry compared to Caucasian women

Abstract

PurposeTriple-negative breast cancer (TNBC) is most prevalent in young women of African ancestry (WAA) compared to women of other ethnicities. Recent studies found a correlation between high expression of the transcription factor Kaiso, TNBC aggressiveness, and ethnicity. However, little is known about Kaiso expression and localization patterns in TNBC tissues of WAA. Herein, we analyze Kaiso expression patterns in TNBC tissues of African (Nigerian), Caribbean (Barbados), African American (AA), and Caucasian American (CA) women.MethodsFormalin-fixed and paraffin embedded (FFPE) TNBC tissue blocks from Nigeria and Barbados were utilized to construct a Nigerian/Barbadian tissue microarray (NB-TMA). This NB-TMA and a commercially available TMA comprising AA and CA TNBC tissues (AA-CA-YTMA) were subjected to immunohistochemistry to assess Kaiso expression and subcellular localization patterns, and correlate Kaiso expression with TNBC clinical features.ResultsNigerian and Barbadian women in our study were diagnosed with TNBC at a younger age than AA and CA women. Nuclear and cytoplasmic Kaiso expression was observed in all tissues analyzed. Analysis of Kaiso expression in the NB-TMA and AA-CA-YTMA revealed that nuclear Kaiso H scores were significantly higher in Nigerian, Barbadian, and AA women compared with CA women. However, there was no statistically significant difference in nuclear Kaiso expression between Nigerian versus Barbadian women, or Barbadian versus AA women.ConclusionsHigh levels of nuclear Kaiso expression were detected in patients with a higher degree of African heritage compared to their Caucasian counterparts, suggesting a role for Kaiso in TNBC racial disparity.Electronic supplementary materialThe online version of this article (doi:10.1007/s10552-017-0955-2) contains supplementary material, which is available to authorized users.

Cancer health disparities in racial/ethnic minorities in the United States

“…[156][157][158][159][160]162 Most of these findings are more evident for young, HRpatients. 155,158,161 Other features, such as a differential mutational landscape 157,163 and higher frequency of DNA copy number alterations, 161 have been reported for AA/Bs compared with NHWs, in addition to the existence of differential immune and inflammatory pathways involved in tumour-specific immune responses between the two groups. 164,165 As stated above, obesity is associated with increased circulating levels of insulin and inflammatory cytokines, such as IL-6, IL-8 and TNF-α and CD8 + T cells and M1 macrophages, which contribute to the development of a pro-tumorigenic microenvironment and more aggressive tumour characteristics, leading to TNBC biology in AA/B women.…”

“…Differences in tumour biology according to race/ethnicity have also been described. Studies have found differences in gene expression [155][156][157] and methylation patterns [158][159][160][161] between AA/Bs and NHWs, which might have a potential impact on patient outcomes. [156][157][158][159][160]162 Most of these findings are more evident for young, HRpatients.…”

Dancing from bottoms up – Roles of the POZ-ZF transcription factor Kaiso in Cancer

“…As a first step in testing this hypothesis, the Daniel and Yates labs independently examined a cohort of breast cancer patients and observed that nuclear Kaiso is significantly overexpressed in breast tumor tissues of patients with an African ancestry [13, 99]. Jones et al further observed that nuclear Kaiso was overexpressed in primary tumor and paired lymph node metastases of AA women compared to Caucasian women (CaW) [13], and AA women with nuclear Kaiso had a decreased overall survival compared to CaW with nuclear Kaiso expression.…”

“…These patient cohorts were selected based on the premise that they represent more homogeneous populations of African ancestry than African Americans. Bassey-Archibong et al found that Nigerian and Barbadian women were diagnosed with TNBC at much younger ages than AA and CauW [99], and that nuclear Kaiso levels were significantly higher in Nigerian, Barbadian and AA women compared with CauW. The high levels of nuclear Kaiso expression in women of African Ancestry compared to their Caucasian counterparts, suggests a role for Kaiso in TNBC racial disparity, and forms the premise for ongoing studies in the Daniel lab to further decipher this phenomenon.…”

Effect of apigenin on whole transcriptome profile of TNFα‑activated MDA‑MB‑468 triple negative breast cancer cells

“…Limited therapeutic options are available for TNBC patients and consequently can result in aggressive metastatic disease, with greater mortality rates in African American (AA) women, relative to Caucasian-American (33,34). This health disparity may arise due to diagnosis at later stages of the disease (35) or a predisposed racially distinct genetic or epigenetic profile (36,37) with a propensity toward an overactive oncogenic p38 MAPK, Wnt/β-catenin, IGF2/ERbeta signaling axis (38)(39)(40). Additional factors to a health disparity arising in AA women regarding TNBC include vitamin D deficiencies (41) socioeconomic factors, later stage diagnosis, obesity, or even breast feeding patterns (42)(43)(44).…”