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      Circular RNAs and RNA Splice Variants as Biomarkers for Prognosis and Therapeutic Response in the Liquid Biopsies of Lung Cancer Patients

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          Abstract

          Lung cancer, including non-small cell lung carcinoma (NSCLC), is the most frequently diagnosed cancer. It is also the leading cause of cancer-related mortality worldwide because of its late diagnosis and its resistance to therapies. Therefore, the identification of biomarkers for early diagnosis, prognosis, and monitoring of therapeutic response is urgently needed. Liquid biopsies, especially blood, are considered as promising tools to detect and quantify circulating cancer biomarkers. Cell-free circulating tumor DNA has been extensively studied. Recently, the possibility to detect and quantify RNAs in tumor biopsies, notably circulating cell-free RNAs, has gained great attention. RNA alternative splicing contributes to the proteome diversity through the biogenesis of several mRNA splice variants from the same pre-mRNA. Circular RNA (circRNA) is a new class of RNAs resulting from pre-mRNA back splicing. Owing to the development of high-throughput transcriptomic analyses, numerous RNA splice variants and, more recently, circRNAs have been identified and found to be differentially expressed in tumor patients compared to healthy controls. The contribution of some of these RNA splice variants and circRNAs to tumor progression, dissemination, or drug response has been clearly demonstrated in preclinical models. In this review, we discuss the potential of circRNAs and mRNA splice variants as candidate biomarkers for the prognosis and the therapeutic response of NSCLC in liquid biopsies.

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          RNA-Seq of Tumor-Educated Platelets Enables Blood-Based Pan-Cancer, Multiclass, and Molecular Pathway Cancer Diagnostics

          Summary Tumor-educated blood platelets (TEPs) are implicated as central players in the systemic and local responses to tumor growth, thereby altering their RNA profile. We determined the diagnostic potential of TEPs by mRNA sequencing of 283 platelet samples. We distinguished 228 patients with localized and metastasized tumors from 55 healthy individuals with 96% accuracy. Across six different tumor types, the location of the primary tumor was correctly identified with 71% accuracy. Also, MET or HER2-positive, and mutant KRAS, EGFR, or PIK3CA tumors were accurately distinguished using surrogate TEP mRNA profiles. Our results indicate that blood platelets provide a valuable platform for pan-cancer, multiclass cancer, and companion diagnostics, possibly enabling clinical advances in blood-based “liquid biopsies”.
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            Foxo3 circular RNA promotes cardiac senescence by modulating multiple factors associated with stress and senescence responses

            Circular RNAs are a subclass of non-coding RNAs detected within mammalian cells. This study was designed to test the roles of a circular RNA circ-Foxo3 in senescence using in vitro and in vivo approaches.
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              Circular RNAs: splicing's enigma variations.

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                Author and article information

                Contributors
                Journal
                Front Genet
                Front Genet
                Front. Genet.
                Frontiers in Genetics
                Frontiers Media S.A.
                1664-8021
                07 May 2019
                2019
                : 10
                : 390
                Affiliations
                [1] 1INSERM U1209, CNRS UMR5309, Institute for Advanced Biosciences, University Grenoble Alpes , Grenoble, France
                [2] 2Grenoble Hospital , La Tronche, France
                [3] 3Department of Clinical Oncology, Queen Elizabeth Hospital , Kowloon, Hong Kong
                Author notes

                Edited by: Ondrej Slaby, Central European Institute of Technology (CEITEC), Czechia

                Reviewed by: Peter G. Zaphiropoulos, Karolinska Institutet (KI), Sweden; Chi-Ming Wong, The University of Hong Kong, Hong Kong

                *Correspondence: Beatrice Eymin, Beatrice.Eymin@ 123456univ-grenoble-alpes.fr

                This article was submitted to RNA, a section of the journal Frontiers in Genetics

                Article
                10.3389/fgene.2019.00390
                6514155
                31134126
                f36a0b40-d0a1-49fb-8a34-3ebf62a6bc4e
                Copyright © 2019 de Fraipont, Gazzeri, Cho and Eymin.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 30 January 2019
                : 10 April 2019
                Page count
                Figures: 1, Tables: 1, Equations: 0, References: 168, Pages: 15, Words: 0
                Funding
                Funded by: Institut National de la Santé et de la Recherche Médicale 10.13039/501100001677
                Funded by: Centre National de la Recherche Scientifique 10.13039/501100004794
                Funded by: Communauté Université Grenoble Alpes 10.13039/100012953
                Categories
                Genetics
                Review

                Genetics
                cancer biomarkers,circular rnas,liquid biopsies,lung cancer,rna splice variants
                Genetics
                cancer biomarkers, circular rnas, liquid biopsies, lung cancer, rna splice variants

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