Expression of potential biomarkers associated with homologous recombination repair in patients with ovarian or triple-negative breast cancer

Hiroyuki Nomura, Fumio Kataoka, Daisuke Aoki, Hiromitsu Jinno, Yuukou Kitagawa, Yuji Sato, Chris Womack, Helen Wombwell, Darren Hodgson, Mark O'Connor, Chris Harbron, Xiaolu Yin

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

BACKGROUND: Poly(ADP)-ribose polymerase (PARP) inhibitors such as olaparib can induce cell death in cancer cells with homologous recombination (HR) DNA repair deficiencies, such as BRCA1/2 mutations. AIM: To identify prognostic biomarkers of long-term outcomes in cancer patients. METHODS: Immunohistochemistry was used to analyse expression of key HR pathway proteins (ATM, ATR, BRCA1, MDC1, MRE11) and PARP-1 in 100 serous ovarian cancer (SOC) and 100 triple-negative breast cancer (TNBC) tumour samples from Japanese patients. RECIST assessment was used. RESULTS: Patient demographic data and BRCA1/2 mutation status were unavailable. Most proteins listed previously were detected in > 80% of tissue samples, with BRCA1 expression detected in 60-65%. A potential link between BRCA1 expression and overall survival (M stage adjusted) in SOC patients was observed, but was not statistically significant after multiple testing adjustment. Correlations between other biomarker expression and survival were not observed. In TNBC patients, MDC1 staining was associated with progressive disease, but this was not statistically significant; the analysis did not identify significant correlations between biomarker expression and disease control. Limited event numbers prevented assessment of the prognostic value of BRCA1 in TNBC. CONCLUSION: BRCA1 expression may be a candidate for a prognostic biomarker in SOC. Further studies are warranted.

Original languageEnglish
Pages (from-to)145-152
Number of pages8
JournalCancer Biomarkers
Volume16
Issue number1
DOIs
Publication statusPublished - 2016 Jan 18

Fingerprint

Triple Negative Breast Neoplasms
Recombinational DNA Repair
Biomarkers
Ovarian Neoplasms
Ataxia Telangiectasia Mutated Proteins
DNA Repair-Deficiency Disorders
Mutation
Survival
Homologous Recombination
Neoplasms
Cell Death
Immunohistochemistry
Demography
Staining and Labeling
Breast Neoplasms
Proteins

Keywords

  • Biomarker
  • BRCA
  • Breast cancer
  • Ovarian cancer

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Genetics

Cite this

Expression of potential biomarkers associated with homologous recombination repair in patients with ovarian or triple-negative breast cancer. / Nomura, Hiroyuki; Kataoka, Fumio; Aoki, Daisuke; Jinno, Hiromitsu; Kitagawa, Yuukou; Sato, Yuji; Womack, Chris; Wombwell, Helen; Hodgson, Darren; O'Connor, Mark; Harbron, Chris; Yin, Xiaolu.

In: Cancer Biomarkers, Vol. 16, No. 1, 18.01.2016, p. 145-152.

Research output: Contribution to journalArticle

Nomura, Hiroyuki ; Kataoka, Fumio ; Aoki, Daisuke ; Jinno, Hiromitsu ; Kitagawa, Yuukou ; Sato, Yuji ; Womack, Chris ; Wombwell, Helen ; Hodgson, Darren ; O'Connor, Mark ; Harbron, Chris ; Yin, Xiaolu. / Expression of potential biomarkers associated with homologous recombination repair in patients with ovarian or triple-negative breast cancer. In: Cancer Biomarkers. 2016 ; Vol. 16, No. 1. pp. 145-152.
@article{0d864c41d42441bcadd3fdddfc3ce7e0,
title = "Expression of potential biomarkers associated with homologous recombination repair in patients with ovarian or triple-negative breast cancer",
abstract = "BACKGROUND: Poly(ADP)-ribose polymerase (PARP) inhibitors such as olaparib can induce cell death in cancer cells with homologous recombination (HR) DNA repair deficiencies, such as BRCA1/2 mutations. AIM: To identify prognostic biomarkers of long-term outcomes in cancer patients. METHODS: Immunohistochemistry was used to analyse expression of key HR pathway proteins (ATM, ATR, BRCA1, MDC1, MRE11) and PARP-1 in 100 serous ovarian cancer (SOC) and 100 triple-negative breast cancer (TNBC) tumour samples from Japanese patients. RECIST assessment was used. RESULTS: Patient demographic data and BRCA1/2 mutation status were unavailable. Most proteins listed previously were detected in > 80{\%} of tissue samples, with BRCA1 expression detected in 60-65{\%}. A potential link between BRCA1 expression and overall survival (M stage adjusted) in SOC patients was observed, but was not statistically significant after multiple testing adjustment. Correlations between other biomarker expression and survival were not observed. In TNBC patients, MDC1 staining was associated with progressive disease, but this was not statistically significant; the analysis did not identify significant correlations between biomarker expression and disease control. Limited event numbers prevented assessment of the prognostic value of BRCA1 in TNBC. CONCLUSION: BRCA1 expression may be a candidate for a prognostic biomarker in SOC. Further studies are warranted.",
keywords = "Biomarker, BRCA, Breast cancer, Ovarian cancer",
author = "Hiroyuki Nomura and Fumio Kataoka and Daisuke Aoki and Hiromitsu Jinno and Yuukou Kitagawa and Yuji Sato and Chris Womack and Helen Wombwell and Darren Hodgson and Mark O'Connor and Chris Harbron and Xiaolu Yin",
year = "2016",
month = "1",
day = "18",
doi = "10.3233/CBM-150550",
language = "English",
volume = "16",
pages = "145--152",
journal = "Cancer Biomarkers",
issn = "1574-0153",
publisher = "IOS Press",
number = "1",

}

TY - JOUR

T1 - Expression of potential biomarkers associated with homologous recombination repair in patients with ovarian or triple-negative breast cancer

AU - Nomura, Hiroyuki

AU - Kataoka, Fumio

AU - Aoki, Daisuke

AU - Jinno, Hiromitsu

AU - Kitagawa, Yuukou

AU - Sato, Yuji

AU - Womack, Chris

AU - Wombwell, Helen

AU - Hodgson, Darren

AU - O'Connor, Mark

AU - Harbron, Chris

AU - Yin, Xiaolu

PY - 2016/1/18

Y1 - 2016/1/18

N2 - BACKGROUND: Poly(ADP)-ribose polymerase (PARP) inhibitors such as olaparib can induce cell death in cancer cells with homologous recombination (HR) DNA repair deficiencies, such as BRCA1/2 mutations. AIM: To identify prognostic biomarkers of long-term outcomes in cancer patients. METHODS: Immunohistochemistry was used to analyse expression of key HR pathway proteins (ATM, ATR, BRCA1, MDC1, MRE11) and PARP-1 in 100 serous ovarian cancer (SOC) and 100 triple-negative breast cancer (TNBC) tumour samples from Japanese patients. RECIST assessment was used. RESULTS: Patient demographic data and BRCA1/2 mutation status were unavailable. Most proteins listed previously were detected in > 80% of tissue samples, with BRCA1 expression detected in 60-65%. A potential link between BRCA1 expression and overall survival (M stage adjusted) in SOC patients was observed, but was not statistically significant after multiple testing adjustment. Correlations between other biomarker expression and survival were not observed. In TNBC patients, MDC1 staining was associated with progressive disease, but this was not statistically significant; the analysis did not identify significant correlations between biomarker expression and disease control. Limited event numbers prevented assessment of the prognostic value of BRCA1 in TNBC. CONCLUSION: BRCA1 expression may be a candidate for a prognostic biomarker in SOC. Further studies are warranted.

AB - BACKGROUND: Poly(ADP)-ribose polymerase (PARP) inhibitors such as olaparib can induce cell death in cancer cells with homologous recombination (HR) DNA repair deficiencies, such as BRCA1/2 mutations. AIM: To identify prognostic biomarkers of long-term outcomes in cancer patients. METHODS: Immunohistochemistry was used to analyse expression of key HR pathway proteins (ATM, ATR, BRCA1, MDC1, MRE11) and PARP-1 in 100 serous ovarian cancer (SOC) and 100 triple-negative breast cancer (TNBC) tumour samples from Japanese patients. RECIST assessment was used. RESULTS: Patient demographic data and BRCA1/2 mutation status were unavailable. Most proteins listed previously were detected in > 80% of tissue samples, with BRCA1 expression detected in 60-65%. A potential link between BRCA1 expression and overall survival (M stage adjusted) in SOC patients was observed, but was not statistically significant after multiple testing adjustment. Correlations between other biomarker expression and survival were not observed. In TNBC patients, MDC1 staining was associated with progressive disease, but this was not statistically significant; the analysis did not identify significant correlations between biomarker expression and disease control. Limited event numbers prevented assessment of the prognostic value of BRCA1 in TNBC. CONCLUSION: BRCA1 expression may be a candidate for a prognostic biomarker in SOC. Further studies are warranted.

KW - Biomarker

KW - BRCA

KW - Breast cancer

KW - Ovarian cancer

UR - http://www.scopus.com/inward/record.url?scp=84956784110&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84956784110&partnerID=8YFLogxK

U2 - 10.3233/CBM-150550

DO - 10.3233/CBM-150550

M3 - Article

C2 - 26577420

AN - SCOPUS:84956784110

VL - 16

SP - 145

EP - 152

JO - Cancer Biomarkers

JF - Cancer Biomarkers

SN - 1574-0153

IS - 1

ER -