Unit:
Τομέας ΧειρουργικήςLibrary of the School of Health Sciences
Dissertation committee:
Ρηγόπουλος Δημήτριος, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ, Επιβλέπων
Ζωγράφος Γεώργιος: Αναπληρωτής Πρύτανης, Καθηγητής-Διεθυντής Χειρουργικής, Ά Προπαιδευτική Πανεπιστημιακή Κλινική, «Ιπποκράτειο» Γενικό Νοσοκομείο Αθηνών.
Λάζαρης Ανδρέας: Επίκουρος Καθηγητής Παθολογικής Ανατομικής & Γενικής Παθολογίας, Εργαστήριο Παθολογικής Ανατομικής, Ιατρική Σχολή Εθνικού και Καποδιστριακού Πανεπιστημίου Αθηνών
Φλώρα Ζαγουρή: Παθολόγος- Ογκολόγος, Αναπληρώτρια Καθηγήτρια Πανεπιστημιακής Θεραπευτικής κλινικής Νοσοκομείου «Αλεξάνδρα» Γ.Ν.Α , Ιατρική Σχολή Εθνικού και Καποδιστριακού Πανεπιστημίου Αθηνών.
Αλέξανδρος Στρατηγός: Καθηγητής Ά Πανεπιστημιακής Δερματολογικής κλινικής, Νοσοκομείο Δερματικών και Αφροδισίων Νόσων «Ανδρέας Συγγρός».
Βασίλιος Κουλούλιας: Αναπληρωτής Καθηγητής Ακτινοθεραπευτικής Ογκολογίας, ΄Β Εργαστήριο Ακτινολογίας, Πανεπιστήμιο Αθηνών, Π.Γ.Ν «Αττικόν»
Άννα Ζυγογιάννη: Επίκουρη Καθηγήτρια Ακτινοθεραπευτικής Ογκολογίας Ε.Κ.Π.Α , Αρεταίειο Νοσοκομείο
Original Title:
Ειδικά χαρακτηριστικά σε τριπλά αρνητικό καρκίνο μαστού στα ελληνικά δεδομένα, προγνωστικοί και προβλεπτικοί δείκτες της νόσου
Translated title:
Special characteristics of women with triple negative breast cancer in Greece. Predictive markers
Summary:
Triple negative breast cancer (TNBC) represents the most aggressive subtype of breast cancer since it is associated with a high recurrence rate in the first 3 years following the diagnosis and poor outcome. Moreover these patients are often characterized by resistance to hormone therapies or targeted therapies, such as trastuzumab which is mainly attributed to the heterogeneity and the complex biological behavior of TNBC. Although molecular aspects of the TNBC pathogenesis have been largely deciphered, effective prognosis and treatment of TNBC patients still remain a challenging task in the clinical setting of oncology, highlighting thereby the need for identifying novel and more reliable prognostic and predictive markers for TNBC patients.
The understanding of the crucial role of immune checkpoints in facilitating tumor escape, uncovered a new class of potential cancer biomarkers and therapeutic targets. Among the most studied immune checkpoints is the Programmed death ligand-1 (PD-L1) that is expressed on tumor cells or tumor-infiltrating immune cells.miRNAs are a new source of novel molecular biomarkers and lately the intensive study of their clinical value has already yielded fruitful results. Single nucleotide polymorphisms (SNPs) have been implicated in cancer development, prognosis and drug-resistance, often interacting with other factors.
The aim of this study was to examine the presence of miR-34 rs4938723 T>C and PD-L1 rs4143815 C>G polymorphism in 114 formalin fixed paraffin embedded tissues isolated by triple negative breast cancer patients and correlated the single nucleotide polymorphism status with the survival of the patients.
Regarding the miR-34 rs4938723 T>C polymorphism our statistical analysis disclosed that the majority of patients harboring ductal breast carcinoma have the TC or CC genotypes (P=0.020). Moreover the survival of the patients was significantly correlated with the occurrence of the TC or CC alleles (P<0.001). Regarding the correlation of miR-34 polymorphisms with patients' survival we found that women with TC or CC single nucleotide polymorphisms were characterized by shorter disease free survival intervals (P=0.05). Furthermore triple negative breast cancer patients with TC/CC genotype exhibited shorter overall survival intervals as disclosed by Kaplan Meier analysis (P<0.001) and Cox regression analysis (HR= 3.2, %95 CI=2.0-5.5, P=0.008). Stratified Kaplan-Meier analysis showed that the women harboring the TC or CC genotype along with the ductal histology had significantly
shorter survival (P<0.001). This result was also confirmed by Univariate Cox regression analysis, which showed that women ductal breast cancer and TC or CC genotype are of worse prognosis (HR= 2.35, %95 CI= 2.1-4.65, P=0.003).
Regarding the rs4143815 polymorphism of the PD-L1our statistical analysis showed that results the GC genotype was significantly associated with advanced disease stage (P=0.015) and with the disease recurrence (P =0.048). Our survival analysis revealed that women harboring the GC genotype demonstrated (P =0.013) shorter DFS (Disease Free Survival) intervals compared to the CC or GG alleles. Moreover, we found that women with stage III and GC or GG SNPs were characterized by shorter DFS (P =0.002) and OS (Overall Survival) intervals (P <0.001). Cox regression analysis at the univariate level confirmed that these women are characterized by worse prognosis (HR= 7.28, %95 CI=0.21-5.82, P <0.001).
In conclusion we found that the PD-L1 rs4143815 polymorphisms are differentially expressed in TNBCs and that this distribution is associated with markers of unfavorable prognosis and with patients' survival. Moreover we found that the TC and CC alleles of the miR-34 rs4938723 T>C are associated with unfavorable prognosis in triple negative breast cancer patients.
Main subject category:
Health Sciences
Keywords:
Triple negative breast cancer, Molecular markers, Predictive markers, Greek population
Number of references:
184
