Gene expression in triple-negative breast cancer in relation to survival
- 494 Downloads
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.
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.
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.
We identified five genes (EOMES, FA2H, GSPT1, RASGRP1, and SOD2) that may serve as potential prognostic biomarkers and/or therapeutic targets for TNBC.
KeywordsTriple-negative breast cancer TNBC Survival Progression Gene expression
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.
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.
- 14.Lee HJ, Lee JJ, Song IH, Park IA, Kang J, Yu JH et al (2015) Prognostic and predictive value of NanoString-based immune-related gene signatures in a neoadjuvant setting of triple-negative breast cancer: relationship to tumor-infiltrating lymphocytes. Breast Cancer Res Treat 151:619–627CrossRefPubMedGoogle Scholar
- 31.Goel S, Viteri S, Morán T, Coronado C, Dios JLI, Miguel-Lillo B et al (2016) Phase I, dose-escalating study of elisidepsin (Irvalec(®)), a plasma membrane-disrupting marine antitumor agent, in combination with erlotinib in patients with advanced malignant solid tumors. Invest New Drugs 34:75–83CrossRefPubMedGoogle Scholar