Unit:
Faculty of MedicineLibrary of the School of Health Sciences
Dissertation committee:
Παναγιώτης Βλαχογιαννόπουλος, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Μιχαήλ Βουλγαρέλης, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Νικόλαος Σύψας, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Αθανάσιος Πρωτογέρου, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Ευσταθία Καψογεώργου ,Αναπληρώτρια Καθηγήτρια, Ιατρική Σχολή, ΕΚΠΑ
Ανδρέας Γουλές, Επίκουρος Καθηγητής, Ιατρική Σχόλη, ΕΚΠΑ
Κωνσταντίνος Μπαξεβάνης, Ερευνητης Α', Διευθυντής (Γενικό Αντικαρκινικό Νοσοκομείο «Ο Άγιος Σάββας»)
Original Title:
Εγκαθίδρυση νέων προγνωστικών και προβλεπτικών δεικτών για τον καρκίνο του προστάτη
Translated title:
Establishing new prognostic and predictive markers in prostate cancer
Summary:
The major role of the immune system in cancer development and evolution is established. Immune biomarkers for cancer prognosis and prediction, including prostate cancer (PCa), are emerging as essential tools for treatment, assessment and monitoring. Given the heterogeneity of PCa and the diversity of therapeutic treatments applied, intensive efforts have been recently initiated for the establishment personalized approaches also in this type of cancer. As HLA-alleles are essential for an effective antitumor response, their expression could serve as prognostic/predictive biomarkers. Studies in melanoma and ovarian cancer have demonstrated that HLA-A*02 allele expression is correlated with poor clinical outcome. Results from our previous phase I trial of PCa suggested that HLA-A*24 allele expression conferred a better clinical outcome.
Based on these data we evaluated herein the prognostic relevance of both alleles in PCa. First, we have shown (in a 56 patients’ study) that HLA-A*02:01 and HLA-A*24:02 in de novo metastatic prostate cancer (mPCa), have an important role for disease progression. Patients expressing HLA-A*02:01 showed poor clinical outcomes vs. HLA-A*02:01- patients. HLA-A*24:02+ patients progressed slower to castrate resistant PCa (CR) and had increased overall survival (OS). Homozygous HLA-A*02:01+ patients progressed severely to CR, with very short OS. Univariate and multivariate analyses ascribed to both HLA alleles significant prognostic values for the time to progression to CR and OS. The presence of HLA-A*02:01 and HLA-A*24:02 alleles in de novo mPCa patients are significantly and independently associated with unfavorable or favorable clinical outcomes, respectively. We also provided evidence to suggest that patients with localized PCa at diagnosis, expressing HLA-A*24:02 had the best clinical outcome in terms of early biochemical recurrence (early BCR) whereas HLA-A*02:01+ showed poor clinical outcome. Furthermore, we made comparisons between our study population (n=237) and population without PCa (n=612). We found out that there is no statistically significant difference, neither in the frequency of the alleles, nor in the percentage of individuals expressing the alleles.
Our data underline HLA-A alleles as valuable prognostic/predictive biomarkers for PCa to assist for the appropriate treatment and follow-up schedule based on the risk for disease progression so to avoid under-treatment and over-treatment.
Main subject category:
Health Sciences
Keywords:
Alleles, HLA, Prostate cancer, Biomarkers, Prognosis
Number of references:
105
File:
File access is restricted until 2024-06-05.
Stokidis_Savvas_PhD.pdf
8 MB
File access is restricted until 2024-06-05.
