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CLCA2 expression is associated with survival among African American women with triple negative breast cancer
PURPOSE: Black/African American (AA) women are twice as likely to be diagnosed with triple negative breast cancer (TNBC) compared to whites, an aggressive breast cancer subtype associated with poor prognosis. There are no routinely used targeted clinical therapies for TNBC; thus there is a clear nee...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7161959/ https://www.ncbi.nlm.nih.gov/pubmed/32298355 http://dx.doi.org/10.1371/journal.pone.0231712 |
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author | Purrington, Kristen S. Knight, Jimmie Dyson, Gregory Ali-Fehmi, Rouba Schwartz, Ann G. Boerner, Julie L. Bandyopadhyay, Sudeshna |
author_facet | Purrington, Kristen S. Knight, Jimmie Dyson, Gregory Ali-Fehmi, Rouba Schwartz, Ann G. Boerner, Julie L. Bandyopadhyay, Sudeshna |
author_sort | Purrington, Kristen S. |
collection | PubMed |
description | PURPOSE: Black/African American (AA) women are twice as likely to be diagnosed with triple negative breast cancer (TNBC) compared to whites, an aggressive breast cancer subtype associated with poor prognosis. There are no routinely used targeted clinical therapies for TNBC; thus there is a clear need to identify prognostic markers and potential therapeutic targets. METHODS: We evaluated expression of 27,016 genes in 155 treatment-naïve TN tumors from AA women in Detroit. Associations with survival were evaluated using Cox proportional hazards models adjusting for stage and age at diagnosis, and p-values were corrected using a false discovery rate. Our validation sample consisted of 494 TN tumors using four publically available data sets. Meta-analyses were performed using summary statistics from the four validation results. RESULTS: In the Detroit AA cohort, CLCA2 [Hazard ratio (HR) = 1.56, 95% confidence interval (CI) 1.31–1.86, nominal p = 5.1x10-7, FDR p = 0.014], SPIC [HR = 1.47, 95%CI 1.26–1.73, nominal p = 1.8x10-6, FDR p = 0.022], and MIR4311 [HR = 1.57, 95% CI 1.31–1.92, nominal p = 2.5x10-5, FDR p = 0.022] expression were associated with overall survival. Further adjustment for treatment and breast cancer specific survival analysis did not substantially alter effect estimates. CLCA2 was also associated with increased risk of death in the validation cohorts [HR = 1.14, 95% CI 1.05–1.24, p = 0.038, p-heterogeneity = 0.88]. CONCLUSIONS: We identified CLCA2 as a potential prognostic marker for TNBC in AA women. |
format | Online Article Text |
id | pubmed-7161959 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-71619592020-04-21 CLCA2 expression is associated with survival among African American women with triple negative breast cancer Purrington, Kristen S. Knight, Jimmie Dyson, Gregory Ali-Fehmi, Rouba Schwartz, Ann G. Boerner, Julie L. Bandyopadhyay, Sudeshna PLoS One Research Article PURPOSE: Black/African American (AA) women are twice as likely to be diagnosed with triple negative breast cancer (TNBC) compared to whites, an aggressive breast cancer subtype associated with poor prognosis. There are no routinely used targeted clinical therapies for TNBC; thus there is a clear need to identify prognostic markers and potential therapeutic targets. METHODS: We evaluated expression of 27,016 genes in 155 treatment-naïve TN tumors from AA women in Detroit. Associations with survival were evaluated using Cox proportional hazards models adjusting for stage and age at diagnosis, and p-values were corrected using a false discovery rate. Our validation sample consisted of 494 TN tumors using four publically available data sets. Meta-analyses were performed using summary statistics from the four validation results. RESULTS: In the Detroit AA cohort, CLCA2 [Hazard ratio (HR) = 1.56, 95% confidence interval (CI) 1.31–1.86, nominal p = 5.1x10-7, FDR p = 0.014], SPIC [HR = 1.47, 95%CI 1.26–1.73, nominal p = 1.8x10-6, FDR p = 0.022], and MIR4311 [HR = 1.57, 95% CI 1.31–1.92, nominal p = 2.5x10-5, FDR p = 0.022] expression were associated with overall survival. Further adjustment for treatment and breast cancer specific survival analysis did not substantially alter effect estimates. CLCA2 was also associated with increased risk of death in the validation cohorts [HR = 1.14, 95% CI 1.05–1.24, p = 0.038, p-heterogeneity = 0.88]. CONCLUSIONS: We identified CLCA2 as a potential prognostic marker for TNBC in AA women. Public Library of Science 2020-04-16 /pmc/articles/PMC7161959/ /pubmed/32298355 http://dx.doi.org/10.1371/journal.pone.0231712 Text en © 2020 Purrington et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Purrington, Kristen S. Knight, Jimmie Dyson, Gregory Ali-Fehmi, Rouba Schwartz, Ann G. Boerner, Julie L. Bandyopadhyay, Sudeshna CLCA2 expression is associated with survival among African American women with triple negative breast cancer |
title | CLCA2 expression is associated with survival among African American women with triple negative breast cancer |
title_full | CLCA2 expression is associated with survival among African American women with triple negative breast cancer |
title_fullStr | CLCA2 expression is associated with survival among African American women with triple negative breast cancer |
title_full_unstemmed | CLCA2 expression is associated with survival among African American women with triple negative breast cancer |
title_short | CLCA2 expression is associated with survival among African American women with triple negative breast cancer |
title_sort | clca2 expression is associated with survival among african american women with triple negative breast cancer |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7161959/ https://www.ncbi.nlm.nih.gov/pubmed/32298355 http://dx.doi.org/10.1371/journal.pone.0231712 |
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