Tumor microRNAs Identified by Small RNA Sequencing as Potential
Response Predictors in Locally Advanced Rectal Cancer Patients
Treated With Neoadjuvant Chemoradiotherapy

J 2020

Tumor microRNAs Identified by Small RNA Sequencing as Potential Response Predictors in Locally Advanced Rectal Cancer Patients Treated With Neoadjuvant Chemoradiotherapy

MACHÁČKOVÁ, Táňa, Karolína TRACHTOVÁ, Vladimír PROCHÁZKA, Tomáš GROLICH, Martina FARKAŠOVÁ et. al.

Basic information

Original name

Tumor microRNAs Identified by Small RNA Sequencing as Potential Response Predictors in Locally Advanced Rectal Cancer Patients Treated With Neoadjuvant Chemoradiotherapy

Authors

MACHÁČKOVÁ, Táňa (203 Czech Republic, belonging to the institution), Karolína TRACHTOVÁ (203 Czech Republic, belonging to the institution), Vladimír PROCHÁZKA (203 Czech Republic, belonging to the institution), Tomáš GROLICH (203 Czech Republic, belonging to the institution), Martina FARKAŠOVÁ (703 Slovakia, belonging to the institution), Lukáš FIALA (203 Czech Republic), Roman ŠEFR (203 Czech Republic), Igor KISS (203 Czech Republic), Matej SKROVINA (203 Czech Republic), Michal DOSOUDIL (203 Czech Republic), Ioana BERINDAN-NEAGOE (642 Romania), Marek SVOBODA (203 Czech Republic), Ondřej SLABÝ (203 Czech Republic, guarantor, belonging to the institution) and Zdeněk KALA (203 Czech Republic, belonging to the institution)

Edition

CANCER GENOMICS & PROTEOMICS, ATHENS, INT INST ANTICANCER RESEARCH, 2020, 1109-6535

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30204 Oncology

Country of publisher

Greece

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 4.069

RIV identification code

RIV/00216224:14740/20:00118648

Organization unit

Central European Institute of Technology

DOI

http://dx.doi.org/10.21873/cgp.20185

UT WoS

000530098500004

Keywords in English

Rectal cancer; chemoradiotherapy; microRNA; prediction

Abstract

V originále

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.

Links

NV16-31765A, research and development project

Name: Využití tkáňových/cirkulujících mikroRNA pro predikci léčebné odpovědi a zpřesnění restagingu karcinomu rekta po neoadjuvantní léčbě

Citovat

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 and Zdeněk KALA. Tumor microRNAs Identified by Small RNA Sequencing as Potential Response Predictors in Locally Advanced Rectal Cancer Patients Treated With Neoadjuvant Chemoradiotherapy. CANCER GENOMICS & PROTEOMICS. ATHENS: INT INST ANTICANCER RESEARCH, 2020, vol. 17, No 3, p. 249-257. ISSN 1109-6535. Available from: https://dx.doi.org/10.21873/cgp.20185.

@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 and 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, 2020, vol.~17, No~3, p.~249-257. ISSN~1109-6535. Available from: https://dx.doi.org/10.21873/cgp.20185.

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