Unit:
Faculty of MedicineLibrary of the School of Health Sciences
Author:
Makrantonakis Andreas-Evangelos
Dissertation committee:
Κωνσταντίνος Δημητρακάκης, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Γεώργιος Ζωγράφος, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Κωνσταντίνος Τούτουζας, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Φλώρα Ζαγουρή, Καθηγήτρια, Ιατρική Σχολή, ΕΚΠΑ
Χρήστος Παπαδημητρίου, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Μαρία Γαζούλη Καθηγήτρια, Ιατρική Σχολή, ΕΚΠΑ
Μιχαήλ Λιόντος Επίκουρος, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Original Title:
Η προβλεπτική αξία των πολυμορφισμών στον τριπλά αρνητικό καρκίνο του μαστού
Translated title:
The predictive value of polymorphisms in triple negative breast cancer
Summary:
In this study we aimed to investigate the prognostic role of the rs822336 G>C and rs822337 T>A polymorphism of the PD-L1 (Programmed death-Ligand 1) in Triple Negative Breast Cancer (TNBC) patients. For the aims of this study FFPEs (Formalin Fixed Paraffin Embedded) tissues from 114 TNBC patients and blood samples from 124 healthy donors were genotyped and subsequently extensive statistical analysis was performed in order to investigate the clinical value of these polymorphism in triple negative breast cancer. Regarding the rs822336 G>C we found that the CG genotype was the most common among women that harbored Stage IV breast tumors (81.8%; p=0.022), recurred (38.9%; p=0.02) and died (66.7%; p=0.04). Similarly, the rs822337 T>A genotype AA is associated with worse prognosis since it was the most common genotype among stage IV tumors (72.7%;p=0.04) and in TNBC patients that relapsed (75%;p=0.021) and died (81.5%; p=0.004). Our statistical analysis revealed that the rs822336 G>C genotype CG and the rs822337 T>A allele AA are strongly associated with inferior DFS (Kaplan-Meier analysis; p=0.002 and p=0.024 respectively, Cox analysis; p=0.005 and p=0.04 respectively) and OS (Kaplan-Meier analysis; p=0.009 and p=0.004 respectively, Cox analysis; p=0.018 and p=0.01 respectively) intervals. Moreover, it was revealed that women harboring mutated genotypes of both SNPs
had shorter disease-free (Kaplan-Meier; p=0.037, Cox analysis; p=0.04) and overall (Kaplan-Meier; p=0.025, Cox analysis; p=0.03) survival compared to patients having normal genotype of at least one SNP. Multivariate analysis also showed that the presence of mutated genotypes of both SNPs is a strong and independent marker for predicting shorter DFS (p =0.02) and OS (p = 0.008). According to our results PD-L1 rs822336 G>C andrs822337 T>A polymorphisms are differentially expressed in TNBCs and this distribution is associated with markers of unfavorable prognosis and with worse patients' survival.
Main subject category:
Health Sciences
Keywords:
PDL1 polymorphisms, Clinical oncology, Breast cancer, Tripple negative breast cancer, Prediction, Prognostic factors, Research, Polymorphisms rs822336 G>C and rs822337 T>A,PCR
Number of references:
100
