Unit:
Faculty of MedicineLibrary of the School of Health Sciences
Author:
Lampropoulou Dimitra-Ioanna
Dissertation committee:
Χρήστος Παπαδημητρίου, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Μαρία Γαζούλη, Καθηγήτρια, Ιατρική Σχολή, ΕΚΠΑ
Θεοδόσιος Θεοδοσόπουλος, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Γεώργιος Θεοδωρόπουλος, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Ιωάννης Κόντης, Αναπληρωτής Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Ιωάννης Παπακωνσταντίνου, Αναπληρωτής Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Δημήτριος Φιλίππου, Επίκουρος Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Original Title:
MicroRNΑs και long non-coding RNAs ως βιοδείκτες στην πρόβλεψη της φαρμακευτικής ανταπόκρισης ασθενών με μεταστατικό ορθοκολικό καρκίνο
Translated title:
MicroRNAs and long non-coding RNAs as treatment response biomarkers in patients suffering from metastatic Colorectal cancer
Summary:
The aim of this study was to investigate a possible correlation between non-coding RNA mononucleotide polymorphisms (SNPs) and response to treatment in patients suffering from metastatic colorectal cancer (mCRC) treated with irinotecan-based regimens.
Patients, Materials and Methods: The investigation of microRNA polymorphisms was performed in genomic DNA isolated from peripheral blood samples from 105 patients, while the investigation of lncRNA polymorphisms in genomic DNA isolated from the peripheral blood of 98 patients with mCRC. Genomic DNA isolation was performed with the NucleoSpin Blood Kit (Macherey-Nagel, Germany). Rs11134527 miR-218 and rs1834306 miR-100 polymorphisms were genotyped using PCR (Polymerase chain Reaction) -RFLP (Restriction Fragment Length Polymorphism) technique. Genotyping of the long non-coding RNA polymorphisms (HOTAIR rs4759314 and MALAT1 rs3200401) was performed with AS (Allele Specific) -PCR. Statistical analysis: The chi-square test with Yate;s correction was used to compare the observed genotype frequencies. Haplotype analysis was performed using the online platform https://www.snpstats.net/preproc.php.
Results: MicroRNA polymorphism substudy - No statistically significant correlations were observed between the objective response and the genotypes under investigation. However, miR-218 rs11134527 GA and AA genotypes and miR-100 rs1834306 CT and TT genotypes were significantly correlated with the subgroup of patients showing disease progression. No statistically significant correlations were observed between the genotypes under study and risk of toxicity development. Rs11134527 GA and AA genotypes were statistically associated with worse prognosis. Similarly, rs1834306 CT and TT were associated with statistically lower overall survival. Long non-coding RNA polymorphism substudy - No significant correlations were found between response and rs4759314 and rs3200401 genotypes and haplotypes. Carriers of rs4759314 AG and GG genotypes is likely to also carry KRAS mutations. A statistically significant correlation was found between rs3200401 CT/TT alleles and toxicity development. No statistically significant correlations were observed between rs4759314 polymorphism and overall survival. However, rs3200401 CT and TT genotypes were significantly associated with lower overall survival.
Conclusions: The present study has shown, for the first time, a possible association between miR-218 rs11134527 and miR-100 rs1834306 polymorphisms and response to treatment regimens including irinotecan. Also, both carriers of the mutant A allele of miR-218 rs11134527 and mutant T allele of miR-100 rs1834306 may not respond to irinotecan-based schemes. In addition, rs11134527 GA/AA and rs1834306 CT/TT genotypes were significantly correlated with lower overall survival. Moreover, it was found that rs3200401 MALAT1 polymorphism, may be correlated with both toxicity development and decreased overall survival. Finally, gene expression analysis showed that rs4759314 HOTAIR mutant G allele carriers may also carry KRAS mutations. Our results need further evaluation by larger-scale studies, so that the polymorphisms under investigation can be used for therapeutic and prognostic purposes in the future.
Main subject category:
Health Sciences
Keywords:
Colorectal cancer, microRNAs, Long non-coding RNAs, Treatment response, Irinotecan, Single Nucleotide Polymorphisms (SNPs)
Number of references:
257
