title: Mesothelin expression is associated with poor outcomes in breast cancer.
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.
authors.affiliation: Medical Scientist Training Program; Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Yun R
authors.initials: YR
authors.lastname: Li
authors.forename: Rena R
authors.initials: RR
authors.lastname: Xian
authors.forename: Amy
authors.initials: A
authors.lastname: Ziober
authors.forename: Jose
authors.initials: J
authors.lastname: Conejo-Garcia
authors.forename: Alfredo
authors.initials: A
authors.lastname: Perales-Puchalt
authors.forename: Carl H
authors.initials: CH
authors.lastname: June
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Zhang
authors.forename: Julia
authors.initials: J
authors.lastname: Tchou
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality* / Q000473:pathology; D015331:Cohort Studies; D018572:Disease-Free Survival; D005260:Female; D058851:GPI-Linked Proteins / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053208:Kaplan-Meier Estimate; D008198:Lymph Nodes / Q000473:pathology; D000090204:Mesothelin; D008875:Middle Aged; D011379:Prognosis; D064726:Triple Negative Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000401:mortality / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; D058851:GPI-Linked Proteins; D000090204:Mesothelin