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

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00209805%3A_____%2F20%3A00078397" target="_blank" >RIV/00209805:_____/20:00078397 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/65269705:_____/20:00072719 RIV/00216224:14740/20:00118648

Výsledek na webu

<a href="http://cgp.iiarjournals.org/content/17/3/249.full.pdf+html" target="_blank" >http://cgp.iiarjournals.org/content/17/3/249.full.pdf+html</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.21873/cgp.20185" target="_blank" >10.21873/cgp.20185</a>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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&lt;0.0006, AUC=0.766). Gene Ontology (GO) clustering and pathway enrichment analysis of the miR-487a-3p mRNA targets, revealed potential mechanisms behind miR-487a-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.

Název v anglickém jazyce

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

Popis výsledku anglicky

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&lt;0.0006, AUC=0.766). Gene Ontology (GO) clustering and pathway enrichment analysis of the miR-487a-3p mRNA targets, revealed potential mechanisms behind miR-487a-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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30204 - Oncology

Projekt

<a href="/cs/project/NV16-31765A" target="_blank" >NV16-31765A: Využití tkáňových/cirkulujících mikroRNA pro predikci léčebné odpovědi a zpřesnění restagingu karcinomu rekta po neoadjuvantní léčbě</a><br>

Návaznosti

—

Rok uplatnění

2020

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Cancer genomics &amp; proteomics

ISSN

1109-6535

e-ISSN

—

Svazek periodika

17

Číslo periodika v rámci svazku

3

Stát vydavatele periodika

GR - Řecká republika

Počet stran výsledku

9

Strana od-do

249-257

Kód UT WoS článku

000530098500004

EID výsledku v databázi Scopus

2-s2.0-85084169925