Mesothelin expression is associated with poor outcomes in breast cancer

Yun R. Li, Rena Xian, Amy Ziober, Jose Conejo-Garcia, Alfredo Perales-Puchalt, Carl H. June, Paul J. Zhang, Julia Tchou

Research output: Contribution to journalArticle

Abstract

Mesothelin is a potential therapeutic target and prognostic marker in breast cancer. However, results on its prognostic value in breast cancer have been equivocal and warranted further evaluation. We analyzed clinical data from two breast cancer patient cohorts comprising of 141 patients treated at our institution (discovery cohort) and 844 patients from The Cancer Genome Atlas (TCGA) (validation cohort). Mesothelin expression was quantified by immunohistochemistry or by RNA transcript levels as measured by whole-transcriptome sequencing in the discovery and validation cohorts respectively. Univariate analyses of data from the discovery cohort demonstrated that tumor size [hazard ratio (HR) = 1.30, 95 % confidence interval (CI) 1.11–1.51], positive (+) axillary lymph nodes (HR = 3.34; 95 % CI 1.51–7.39), and mesothelin expression (HR = 2.03; 95 % CI 1.10–3.74) were associated with disease-specific survival. Multivariate analyses demonstrated that mesothelin expression was significantly associated with worse survival (HR = 3.06, 95 % CI 1.40–6.68) after adjusting for (+) axillary lymph nodes and tumor size. Using TCGA cohort as validation dataset, mesothelin-expressing tumors were indeed significantly associated with worse overall survival with HR = 1.46; 95 % CI 1.05–2.03 and HR = 1.69; 95 % CI 1.17–2.42 in univariate and multivariate analyses respectively. Our results suggest that mesothelin is a prognostic breast tumor marker whose expression is highly enriched in triple negative breast cancer (TNBC) tumors. As there is no existing targeted therapy for TNBC, mesothelin may be a promising drug target for TNBC. Future work is needed to evaluate the efficacy of mesothelin directed targeted therapy in the treatment of breast cancer.

Original languageEnglish (US)
Pages (from-to)675-684
Number of pages10
JournalBreast Cancer Research and Treatment
Volume147
Issue number3
DOIs
StatePublished - Jan 1 2014

Fingerprint

Breast Neoplasms
Confidence Intervals
Triple Negative Breast Neoplasms
Atlases
Neoplasms
Survival
Multivariate Analysis
Lymph Nodes
Genome
mesothelin
Therapeutics
Tumor Biomarkers
Transcriptome
Immunohistochemistry
RNA
Pharmaceutical Preparations

Keywords

  • Basal tumor subtype
  • Breast cancer outcome
  • Breast cancer subtype
  • Mesothelin
  • Targeted therapy
  • Triple negative breast cancer (TNBC)
  • Tumor marker

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Li, Y. R., Xian, R., Ziober, A., Conejo-Garcia, J., Perales-Puchalt, A., June, C. H., ... Tchou, J. (2014). Mesothelin expression is associated with poor outcomes in breast cancer. Breast Cancer Research and Treatment, 147(3), 675-684. https://doi.org/10.1007/s10549-014-3077-5

Mesothelin expression is associated with poor outcomes in breast cancer. / Li, Yun R.; Xian, Rena; Ziober, Amy; Conejo-Garcia, Jose; Perales-Puchalt, Alfredo; June, Carl H.; Zhang, Paul J.; Tchou, Julia.

In: Breast Cancer Research and Treatment, Vol. 147, No. 3, 01.01.2014, p. 675-684.

Research output: Contribution to journalArticle

Li, YR, Xian, R, Ziober, A, Conejo-Garcia, J, Perales-Puchalt, A, June, CH, Zhang, PJ & Tchou, J 2014, 'Mesothelin expression is associated with poor outcomes in breast cancer', Breast Cancer Research and Treatment, vol. 147, no. 3, pp. 675-684. https://doi.org/10.1007/s10549-014-3077-5
Li, Yun R. ; Xian, Rena ; Ziober, Amy ; Conejo-Garcia, Jose ; Perales-Puchalt, Alfredo ; June, Carl H. ; Zhang, Paul J. ; Tchou, Julia. / Mesothelin expression is associated with poor outcomes in breast cancer. In: Breast Cancer Research and Treatment. 2014 ; Vol. 147, No. 3. pp. 675-684.
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