Study of kallikrein and L-Dopa decarboxylase gene expression regulation through microRNA molecules, in breast cancer: Evaluation of their differential diagnostic potential, and prognostic and predictive value.

Doctoral Dissertation uoadl:1309104 472 Read counter

Unit:
Τομέας Βιοχημείας Μοριακής Βιολογίας
Library of the School of Science
Deposit date:
2015-11-25
Year:
2015
Author:
Μιχαηλίδου Κλείτα
Dissertation committee:
Σκορίλας Ανδρέας, Καθηγητής Τμήματος Βιολογίας, Ε.Κ.Π.Α. (Επιβλέπων), Φραγκούλης Γ. Εμμανουήλ, Ομότ. Καθηγητής Τμήματος Βιολογίας, Ε.Κ.Π.Α., Σίδερης Διαμάντης, Αναπλ. Καθηγητής Τμήματος Βιολογίας, Ε.Κ.Π.Α.
Original Title:
Μελέτη της ρύθμισης της γονιδιακής έκφρασης των καλλικρεϊνών και της L-DOPA αποκαρβοξυλάσης, μέσω μορίων microRNA, στον καρκίνο του μαστού: Αξιολόγηση της διαφοροδιαγνωστικής, προβλεπτικής και προγνωστικής αξίας.
Languages:
Greek
Translated title:
Study of kallikrein and L-Dopa decarboxylase gene expression regulation through microRNA molecules, in breast cancer: Evaluation of their differential diagnostic potential, and prognostic and predictive value.
Summary:
Aim of the study: The expression analysis and clinical evaluation of KLK8 and
DDC, as well as the microRNA molecules which target the genes of interest,
miR-224 and miR-145.
Materials and Methods: Breast tissues (cancerous and non-cancerous, N=250) were
homogenized and total RNA was extracted, polyadenylated (for miRNA analyses)
and reverse transcribed into cDNA. Using different miRNA target prediction
algorithms, we selected for further analysis two miRNAs, miR-224 and miR-145.
Thereafter, KLK8, DDC as well as miR-224 and miR-145 expression levels, were
quantified using Real-Time PCR. The clinical evaluation of the prognostic and
the differential diagnostic potential of the biomolecules under study was
accomplished by using extensive biostatistical analyses.
Results – Conclusion: Multivariate analysis showed that KLK8 expression is a
strong and independent predictor of adverse DFS in breast cancer (HR=4.54,
P=0.004). DDC mRNA levels were increased in a statistically significant degree
in Ki67 positive (P=0.023) and high histological grade breast tumors (P=0.020).
DDC mRNA expression was identified as strong independent indicator of
unfavorable outcome with regard to DFS, for breast cancer patients (HR=3.82,
P=0.033). In the case of miR-224, we observed that high-levels of miR-224
expression, is also a significant unfavorable prognostic marker independent of
other clinicopathological factors (HR=4.86, P=0.014). miR-145, was found to be
lower in high histological grade breast tumors (P<0.001) and in Ki67 positive
ones (P<0.001). It is worth mentioning here, that DDC expression profile was
the exact opposite in breast tumors with these clinicopathological features.
In conclusion, the biomolecules under study, represent promising molecular
indicators that could aid in the differential diagnosis and provide accurate
prognostic information for breast cancer patients.
Keywords:
Breast cancer, Kallikreins/KLKs, L-DOPA Decarboxylase, DDC, microRNAs, Prognostic molecular biomarkers
Index:
No
Number of index pages:
0
Contains images:
Yes
Number of references:
349
Number of pages:
XIV, 228
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