Relationships of protein biomarkers of the urokinase plasminogen activator system with expression of their cognate genes in primary breast carcinomas (original) (raw)

Journal of Clinical Laboratory Analysis

Background: uPA,itsreceptoruPAR,andinhibitorsPAI-1andPAI-2playkeyroles inmembraneremodeling/invasionandinpredictingresponsetochemotherapy.We identified novel relationships of these biomarkers with ER/PR that indicate clinical utility for assessing breast carcinoma outcomes. Methods: Retrospective studies were performed with de-identified results of (a) uPA,uPAR,andPAI-1;(b)estrogen(ER)andprogestinreceptor(PR);and(c)clinical outcomes.Relativeexpressionof22000genesfrommicroarrayofRNAfromLCM-procuredbreastcancercellswasusedwithRStudioversion3.4.1. Results: PrimaryER/PRstatuswasrelatedtouPA,uPAR,orPAI-1levels.ER−orPR− cancers expressed elevated uPA, uPAR, and PAI2 mRNA compared to ER+ or PR+ cells. Inverse relationships between ER/PR protein and expression of uPA, uPAR, and PAI-2 were observed, whereas HER2 status was unrelated. qPCR analyses showed RERG and NQO-1expressionswereelevatedinuPA−lesions,whileCD34 and EDG-1 were elevated in uPAR− cancers. ERBB4 was overexpressed in PAI-1+ carcinomas. Cox regression analyses revealed relationships of ER/PR status and uPA system members with regard to clinical outcomes of breast cancer. Conclusions: uPA, uPAR, PAI1, or PAI2expressionwasincreasedineitherER−orPR− cancerssimilartothatofproteincontentinER−/PR−carcinomas,suggestingsexhor-monesregulatetheuPAsysteminbreastcancer.Resultsrevealedproteincontentof uPAsystemmemberswasrelatedtoER/PRstatusofprimarylesions.UseofLCMprocured carcinoma cells uncovered relationships between expression of known cancer-associatedgenesandproteincontentofuPAsystemmembers.Collectively, results indicate evaluation of ER and PR protein of primary breast cancers combined withanalysesofuPA,uPAR,andPAI-1proteincontentimprovesassessmentofclinical outcomes.