mRNA overexpression of kallikrein-related peptidase 14 (KLK14) is an independent predictor of poor overall survival in chronic lymphocytic leukemia patients

Background: Tissue kallikrein and kallikrein-related peptidases (KLKs) compose a family of serine endopeptidases with much clinical interest in oncology, as their potential as diagnostic and/ or prognostic molecular biomarkers in several human malignancies has already been evidenced. However, none of the members of this family has ever been studied in hematological malignancies. Based on our preliminary results regarding the differential mRNA expression of several KLK genes in peripheral blood mononuclear cells (PBMCs) of patients with chronic lymphocytic leukemia (CLL) compared to healthy blood donors, we decided to study the diagnostic and prognostic potential of KLK14 mRNA expression in CLL. Methods: Total RNA was isolated from 69 CLL patients and 31 non-leukemic blood donors. After reverse transcription of poly(A)-RNA, KLK14 mRNA levels were quantified using a sensitive and accurate quantitative real-time PCR (qPCR) methodology. Results: According to ROC analysis, KLK14 mRNA over-expression successfully discriminated CLL patients from normal population (area under the curve [AUC] 0.89, 95% confidence interval [CI] 0.83-0.95, p < 0.001). Moreover, although not clearly related to clinical staging or other prognostic factors including IGHV mutational status and CD38 expression, strong KLK14 mRNA expression was shown to predict reduced overall survival of CLL patients (p = 0.026) using Kaplan-Meier survival analysis. The unfavorable prognostic value of KLK14 mRNA overexpression in CLL patients' PBMCs was independent of established prognostic factors of the disease, as shown by multivariate Cox regression analysis (hazard ratio [HR] 14.65, 95% CI 1.81-118.36, p = 0.012). Conclusions: KLK14 mRNA expression merits further investigation as a potential prognostic biomarker of overall survival of patients with CLL.