Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Purrington, Kristen S., Knight, Jimmie, Dyson, Gregory, Ali-Fehmi, Rouba, Schwartz, Ann G., Boerner, Julie L., Bandyopadhyay, Sudeshna
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2020
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
_version_ 1783523011023863808
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
work_keys_str_mv AT purringtonkristens clca2expressionisassociatedwithsurvivalamongafricanamericanwomenwithtriplenegativebreastcancer
AT knightjimmie clca2expressionisassociatedwithsurvivalamongafricanamericanwomenwithtriplenegativebreastcancer
AT dysongregory clca2expressionisassociatedwithsurvivalamongafricanamericanwomenwithtriplenegativebreastcancer
AT alifehmirouba clca2expressionisassociatedwithsurvivalamongafricanamericanwomenwithtriplenegativebreastcancer
AT schwartzanng clca2expressionisassociatedwithsurvivalamongafricanamericanwomenwithtriplenegativebreastcancer
AT boernerjuliel clca2expressionisassociatedwithsurvivalamongafricanamericanwomenwithtriplenegativebreastcancer
AT bandyopadhyaysudeshna clca2expressionisassociatedwithsurvivalamongafricanamericanwomenwithtriplenegativebreastcancer