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Breast Cancer Research and Treatment

, Volume 171, Issue 1, pp 199–207 | Cite as

Gene expression in triple-negative breast cancer in relation to survival

  • Shuyang Wang
  • Alicia Beeghly-Fadiel
  • Qiuyin Cai
  • Hui Cai
  • Xingyi Guo
  • Liang Shi
  • Jie Wu
  • Fei Ye
  • Qingchao Qiu
  • Ying Zheng
  • Wei Zheng
  • Ping-Ping Bao
  • Xiao-ou Shu
Epidemiology

Abstract

Purpose

The identification of biomarkers related to the prognosis of triple-negative breast cancer (TNBC) is critically important for improved understanding of the biology that drives TNBC progression.

Methods

We evaluated gene expression in total RNA isolated from formalin-fixed paraffin-embedded tumor samples using the NanoString nCounter assay for 469 TNBC cases from the Shanghai Breast Cancer Survival Study. We used Cox regression to quantify Hazard Ratios (HR) and corresponding confidence intervals (CI) for overall survival (OS) and disease-free survival (DFS) in models that included adjustment for breast cancer intrinsic subtype. Of 302 genes in our discovery analysis, 22 were further evaluated in relation to OS among 134 TNBC cases from the Nashville Breast Health Study and the Southern Community Cohort Study; 16 genes were further evaluated in relation to DFS in 335 TNBC cases from four gene expression omnibus datasets. Fixed-effect meta-analysis was used to combine results across data sources.

Results

Twofold higher expression of EOMES (HR 0.90, 95% CI 0.83–0.97), RASGRP1 (HR 0.89, 95% CI 0.82–0.97), and SOD2 (HR 0.80, 95% CI 0.66–0.96) was associated with better OS. Twofold higher expression of EOMES (HR 0.89, 95% CI 0.81–0.97) and RASGRP1 (HR 0.87, 95% CI 0.81–0.95) was also associated with better DFS. On the contrary, a doubling of FA2H (HR 1.14, 95% CI 1.06–1.22) and GSPT1 (HR 1.33, 95% CI 1.14–1.55) expression was associated with shorter DFS.

Conclusions

We identified five genes (EOMES, FA2H, GSPT1, RASGRP1, and SOD2) that may serve as potential prognostic biomarkers and/or therapeutic targets for TNBC.

Keywords

Triple-negative breast cancer TNBC Survival Progression Gene expression 

Notes

Acknowledgements

This study was supported by grants from the Department of Defense Breast Cancer Research Program (DAMD 17-02-1-0607) and the National Institutes of Health (R01CA118229; P50CA098131). RNA sample preparation was conducted at the Survey and Biospecimen Shared Resources facility that is supported in part by the Vanderbilt-Ingram Cancer Center (P30 CA068485). The authors thank participants and research team members of the Shanghai Breast Cancer Survival Study for their dedication to the study; Ms. Regina Courtney and Dr. Bo Huang for their help with RNA sample preparation.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflicts of interest.

Ethical approval

All participants of the SBCSS, SCCS, and NBHS provided informed consent; institutional approval was garnered from all appropriate review boards, and all experiments were conducted in compliance with relevant federal and state laws.

Supplementary material

10549_2018_4816_MOESM1_ESM.xlsx (41 kb)
Supplementary material 1 (XLSX 41 KB)

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Shuyang Wang
    • 1
  • Alicia Beeghly-Fadiel
    • 1
    • 5
  • Qiuyin Cai
    • 1
  • Hui Cai
    • 1
  • Xingyi Guo
    • 1
  • Liang Shi
    • 2
  • Jie Wu
    • 1
  • Fei Ye
    • 3
  • Qingchao Qiu
    • 1
  • Ying Zheng
    • 4
  • Wei Zheng
    • 1
  • Ping-Ping Bao
    • 2
  • Xiao-ou Shu
    • 1
  1. 1.Division of Epidemiology, Department of MedicineVanderbilt University Medical Center, Vanderbilt-Ingram Cancer CenterNashvilleUSA
  2. 2.Shanghai Municipal Center for Disease Control and PreventionShanghaiChina
  3. 3.Department of BiostatisticsVanderbilt University Medical CenterNashvilleUSA
  4. 4.Shanghai Cancer HospitalFudan UniversityShanghaiChina
  5. 5.Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Institute for Medicine and Public HealthVanderbilt University Medical Center, Vanderbilt-Ingram Cancer CenterNashvilleUSA

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