Τίτλος:
Kallikrein-related peptidase 6 (KLK6) expression differentiates tumor subtypes and predicts clinical outcome in breast cancer patients
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Novel molecular markers that address the heterogeneity of breast cancer (BC) and provide meaningful prognostic information for BC patients are needed. Kallikrein-related peptidase 6 (KLK6) is aberrantly expressed and functionally implicated in BC and, like other members of the KLK family, may prove a useful molecular tool for clinical management. Our objective was to assess, for the first time, the clinical relevance of KLK6 mRNA expression in BC. Total RNA was isolated from 165 breast tumors, as well as 100 adjacent non-cancerous tumor specimens. After cDNA synthesis, and following quality control, quantitative real-time PCR for KLK6 expression analysis took place. Receiver operating characteristic curves were constructed in order to assess the ability of KLK6 mRNA expression levels to differentiate between molecular BC subtypes. Survival analyses, using DFS as endpoint, were performed at the univariate and multivariate levels. Publicly available BC databases and online survival analysis tools were used to validate our findings. A significant downregulation of KLK6 mRNA expression was observed in BC tissue sections compared to the non-cancerous component (P < 0.001). The expression of KLK6 is positively associated with tumor grade (P = 0.038) and is overexpressed in TNBC and HER2-positive tumors (P < 0.001). Aberrant KLK6 expression predicts the clinical outcome of BC patients in terms of DFS, independently of currently used prognostic markers (HR = 7.11, 95% CI = 1.19–42.45). The differential expression of KLK6 and its association with unfavorable outcome in BC patients was validated via in silico analyses. Although an independent external cohort is necessary to confirm our findings, we proved for the first time that KLK6 can provide independent prognostic information for BC patients. © 2018, Springer International Publishing AG, part of Springer Nature.
Συγγραφείς:
Haritos, C.
Michaelidou, K.
Mavridis, K.
Missitzis, I.
Ardavanis, A.
Griniatsos, J.
Scorilas, A.
Περιοδικό:
Advances in Clinical and Experimental Medicine
Εκδότης:
Springer-Verlag Italia s.r.l.
Λέξεις-κλειδιά:
complementary DNA; kallikrein 6; Ki 67 antigen; messenger RNA; kallikrein; KLK6 protein, human, adult; advanced cancer; agar gel electrophoresis; Article; breast cancer; breast tissue; cancer patient; cancer prognosis; cancer staging; cancer surgery; cancer survival; clinical outcome; comparative study; disease association; DNA synthesis; down regulation; female; gene expression; gene overexpression; genetic analysis; human; human tissue; immunohistochemistry; labeling index; major clinical study; mRNA expression level; priority journal; quality control; real time polymerase chain reaction; RNA isolation; survival analysis; aged; breast tumor; cancer grading; down regulation; gene expression regulation; genetics; middle aged; pathology; prognosis; tumor cell line; very elderly, Adult; Aged; Aged, 80 and over; Breast Neoplasms; Cell Line, Tumor; Down-Regulation; Female; Gene Expression Regulation, Neoplastic; Humans; Kallikreins; Middle Aged; Neoplasm Grading; Prognosis; Survival Analysis
DOI:
10.1007/s10238-018-0487-4
