Expression analysis, study and clinical evaluation of kallikrein-related peptidases KLK13 and KLK15 in prostate cancer

Doctoral Dissertation uoadl:1308642 530 Read counter

Unit:
Τομέας Βιοχημείας Μοριακής Βιολογίας
Library of the School of Science
Deposit date:
2013-07-17
Year:
2013
Author:
Μαυρίδης Κωνσταντίνος
Dissertation committee:
Σκορίλας Ανδρέας, Αναπλ. Καθηγητής Τμήματος Βιολογίας, Ε.Κ.Π.Α. (Επιβλέπων), Φραγκούλης Γ. Εμμανουήλ, Καθηγητής Τμήματος Βιολογίας, Ε.Κ.Π.Α., Σίδερης Διαμάντης, Αναπλ. Καθηγητής, Τμήμα Βιολογίας, Ε.Κ.Π.Α.
Original Title:
Ανάλυση της έκφρασης, μελέτη και κλινική αξιολόγηση των καλλικρεϊνών KLK13 και KLK15 στον καρκίνο του προστάτη
Languages:
Greek
Translated title:
Expression analysis, study and clinical evaluation of kallikrein-related peptidases KLK13 and KLK15 in prostate cancer
Summary:
Aim: The expression analysis and clinical evaluation of KLK13, KLK15, and the
KLK15-targeting miR-224 in prostate tumors.
Materials and Methods: Prostate tissues were homogenized and total RNA was
extracted, polyadenylated (for miRNA analyses) and reverse transcribed into
cDNA. KLK13, KLK15, as well as miR-224 expression, was quantified, using
Real-Time PCR. The effects of chemotherapeutic agents on the viability of the
DU145 prostate cancer cells and the expression levels of KLK13 and KLK15 genes
were assessed, via MTT-Trypan blue methods and qPCR, respectively. Extensive
biostatistical analyses were employed (non parametric tests, ROC curve,
Kaplan-Meier survival and univariate/multivariate Cox regression analyses).
Results: KLK13 mRNA levels constitute a novel biomarker of favorable prognosis
(p=0.015). KLK15 mRNA levels are increased in prostate cancer (p<0,001) and are
associated with advanced pathological stages (p=0.023). KLK15 expression was
identified as an independent predictor of disease recurrence (HR=3.36,
p=0.038). MiR-224 expression is decreased in prostate cancer (p<0.001). MiR-224
was identified as a molecular indicator of favorable prognosis (p=0,021). It
was shown that the administration of chemotherapeutic compounds leads to
important modulations in the KLK15 expression.
Conclusions: The studied biomolecules represent promising molecular indicators
that could aid in the differential diagnosis of prostate cancer and provide
accurate prognostic information.
Keywords:
Prostate cancer, Cancer biomarkers, Kallikreins/KLKs, Gene expression analysis, miRNAs
Index:
Yes
Number of index pages:
viii - xiii
Contains images:
Yes
Number of references:
245
Number of pages:
xiii, 218
document.pdf (5 MB) Open in new window