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.

Základní údaje

Originální název

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

Autoři

MACHÁČKOVÁ, Táňa (203 Česká republika, domácí), Karolína TRACHTOVÁ (203 Česká republika, domácí), Vladimír PROCHÁZKA (203 Česká republika, domácí), Tomáš GROLICH (203 Česká republika, domácí), Martina FARKAŠOVÁ (703 Slovensko, domácí), Lukáš FIALA (203 Česká republika), Roman ŠEFR (203 Česká republika), Igor KISS (203 Česká republika), Matej SKROVINA (203 Česká republika), Michal DOSOUDIL (203 Česká republika), Ioana BERINDAN-NEAGOE (642 Rumunsko), Marek SVOBODA (203 Česká republika), Ondřej SLABÝ (203 Česká republika, garant, domácí) a Zdeněk KALA (203 Česká republika, domácí)

Vydání

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

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30204 Oncology

Stát vydavatele

Řecko

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 4.069

Kód RIV

RIV/00216224:14740/20:00118648

Organizační jednotka

Středoevropský technologický institut

DOI

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

UT WoS

000530098500004

Klíčová slova anglicky

Rectal cancer; chemoradiotherapy; microRNA; prediction

Štítky

14110223, 14110230, podil, rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 10. 3. 2021 16:15, Mgr. Pavla Foltynová, Ph.D.

Anotace

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.

Návaznosti

NV16-31765A, projekt VaV

Název: 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 a 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, roč. 17, č. 3, s. 249-257. ISSN 1109-6535. Dostupné z: 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 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, 2020, roč.~17, č.~3, s.~249-257. ISSN~1109-6535. Dostupné z: https://dx.doi.org/10.21873/cgp.20185.

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