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

The result's identifiers

  • Result code in 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>

  • Alternative codes found

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

  • Result on the web

    <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>

Alternative languages

  • Result language

    angličtina

  • Original language name

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

  • Original language description

    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.

  • Czech name

  • Czech description

Classification

  • Type

    J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database

  • CEP classification

  • OECD FORD branch

    30204 - Oncology

Result continuities

  • Project

    <a href="/en/project/NV16-31765A" target="_blank" >NV16-31765A: Utility of tissue/circulating microRNAs for response prediction and improvement of restaging accuracy in rectal cancer after neoadjuvant treatment</a><br>

  • Continuities

Others

  • Publication year

    2020

  • Confidentiality

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

Data specific for result type

  • Name of the periodical

    Cancer genomics &amp; proteomics

  • ISSN

    1109-6535

  • e-ISSN

  • Volume of the periodical

    17

  • Issue of the periodical within the volume

    3

  • Country of publishing house

    GR - GREECE

  • Number of pages

    9

  • Pages from-to

    249-257

  • UT code for WoS article

    000530098500004

  • EID of the result in the Scopus database

    2-s2.0-85084169925