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@article{1744877,
author = {Macháčková, Táňa and Trachtová, Karolína and Procházka, Vladimír and Grolich, Tomáš and Farkašová, Martina and Fiala, Lukáš and Šefr, Roman and Kiss, Igor and Skrovina, Matej and Dosoudil, Michal and BerindanandNeagoe, Ioana and Svoboda, Marek and Slabý, Ondřej and Kala, Zdeněk},
article_location = {ATHENS},
article_number = {3},
doi = {http://dx.doi.org/10.21873/cgp.20185},
keywords = {Rectal cancer; chemoradiotherapy; microRNA; prediction},
language = {eng},
issn = {1109-6535},
journal = {CANCER GENOMICS & PROTEOMICS},
title = {Tumor microRNAs Identified by Small RNA Sequencing as Potential Response Predictors in Locally Advanced Rectal Cancer Patients Treated With Neoadjuvant Chemoradiotherapy},
url = {https://cgp.iiarjournals.org/content/cgp/17/3/249.full.pdf},
volume = {17},
year = {2020}
}
TY - JOUR
ID - 1744877
AU - Macháčková, Táňa - Trachtová, Karolína - Procházka, Vladimír - Grolich, Tomáš - Farkašová, Martina - Fiala, Lukáš - Šefr, Roman - Kiss, Igor - Skrovina, Matej - Dosoudil, Michal - Berindan-Neagoe, Ioana - Svoboda, Marek - Slabý, Ondřej - Kala, Zdeněk
PY - 2020
TI - Tumor microRNAs Identified by Small RNA Sequencing as Potential Response Predictors in Locally Advanced Rectal Cancer Patients Treated With Neoadjuvant Chemoradiotherapy
JF - CANCER GENOMICS & PROTEOMICS
VL - 17
IS - 3
SP - 249-257
EP - 249-257
PB - INT INST ANTICANCER RESEARCH
SN - 11096535
KW - Rectal cancer
KW - chemoradiotherapy
KW - microRNA
KW - prediction
UR - https://cgp.iiarjournals.org/content/cgp/17/3/249.full.pdf
N2 - Background/Aim: Rectal cancer accounts for approximately one-third of all colorectal cancers. Currently, the standard treatment for locally advanced rectal cancer (LARC) is neoadjuvant chemoradiotherapy (CRT) with capecitabine or 5-fluorouracil followed by curative surgery. Unfortunately, only 20% of patients with LARC present complete pathological response after CRT, whereas in 20-40% cases the response is poor or absent. The aim of our study was to evaluate whether microRNAs (miRNAs) in tumor biopsy specimen have the potential to predict therapeutic response in LARC patients. Patients and Methods: In total 87 LARC patients treated by CRT were enrolled in our prospective study. To identify predictive miRNAs, we used small RNA sequencing in 40 tumor biopsy samples of LARC patients (20 responders, 20 non-responders) and qPCR validation of selected miRNA candidates. Results: In the discovery phase of the study, we identified 69 miRNAs to have significantly different expression between the group of responders (TRG 1,2) and a group of non-responders (TRG 4,5) to neoadjuvant CRT. Among these miRNAs, 48 showed a lower expression and 21 showed higher expression in tumor tissues from poorly responding LARC patients. Five miRNAs were selected for validation, but only miR-487a-3p was confirmed to have a significantly higher expression in the tumor biopsy specimens of non-responders to neoadjuvant CRT (p<0.0006, AUC=0.766). Gene Ontology (GO) clustering and pathway enrichment analysis of the miR-487a-3p mRNA targets, revealed potential mechanisms behind miR487a-3p roles in chemoradioresistance (e.g. TGF-beta signaling pathway, protein kinase activity, double-stranded DNA binding, or microRNAs in cancer). Conclusion: By combination of miRNA expression profiling and integrative computational biology we identified miR-487a-3p as a potential predictive biomarker of CRT response in LARC patients.
ER -
MACHÁČKOVÁ, Táňa, Karolína TRACHTOVÁ, Vladimír PROCHÁZKA, Tomáš GROLICH, Martina FARKAŠOVÁ, Lukáš FIALA, Roman ŠEFR, Igor KISS, Matej SKROVINA, Michal DOSOUDIL, Ioana BERINDAN-NEAGOE, Marek SVOBODA, Ondřej SLABÝ a Zdeněk KALA. Tumor microRNAs Identified by Small RNA Sequencing as Potential Response Predictors in Locally Advanced Rectal Cancer Patients Treated With Neoadjuvant Chemoradiotherapy. \textit{CANCER GENOMICS \&{}amp; PROTEOMICS}. ATHENS: INT INST ANTICANCER RESEARCH, roč.~17, č.~3, s.~249-257. ISSN~1109-6535. doi:10.21873/cgp.20185. 2020.
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