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      Improving diagnosis, prognosis and prediction by using biomarkers in CRC patients

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          Abstract

          Colorectal cancer (CRC) is among the most common cancers. In fact, it is placed in the third place among the most diagnosed cancer in men, after lung and prostate cancer, and in the second one for the most diagnosed cancer in women, following breast cancer. Moreover, its high mortality rates classifies it among the leading causes of cancer-related death worldwide. Thus, in order to help clinicians to optimize their practice, it is crucial to introduce more effective tools that will improve not only early diagnosis, but also prediction of the most likely progression of the disease and response to chemotherapy. In that way, they will be able to decrease both morbidity and mortality of their patients. In accordance with that, colon cancer research has described numerous biomarkers for diagnostic, prognostic and predictive purposes that either alone or as part of a panel would help improve patient's clinical management. This review aims to describe the most accepted biomarkers among those proposed for use in CRC divided based on the clinical specimen that is examined (tissue, faeces or blood) along with their restrictions. Lastly, new insight in CRC monitoring will be discussed presenting promising emerging biomarkers (telomerase activity, telomere length and micronuclei frequency).

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          Most cited references158

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          Posttranscriptional regulation of the heterochronic gene lin-14 by lin-4 mediates temporal pattern formation in C. elegans.

          During C. elegans development, the temporal pattern of many cell lineages is specified by graded activity of the heterochronic gene Lin-14. Here we demonstrate that a temporal gradient in Lin-14 protein is generated posttranscriptionally by multiple elements in the lin-14 3'UTR that are regulated by the heterochronic gene Lin-4. The lin-14 3'UTR is both necessary and sufficient to confer lin-4-mediated posttranscriptional temporal regulation. The function of the lin-14 3'UTR is conserved between C. elegans and C. briggsae. Among the conserved sequences are seven elements that are each complementary to the lin-4 RNAs. A reporter gene bearing three of these elements shows partial temporal gradient activity. These data suggest a molecular mechanism for Lin-14p temporal gradient formation: the lin-4 RNAs base pair to sites in the lin-14 3'UTR to form multiple RNA duplexes that down-regulate lin-14 translation.
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            Switching from repression to activation: microRNAs can up-regulate translation.

            AU-rich elements (AREs) and microRNA target sites are conserved sequences in messenger RNA (mRNA) 3' untranslated regions (3'UTRs) that control gene expression posttranscriptionally. Upon cell cycle arrest, the ARE in tumor necrosis factor-alpha (TNFalpha) mRNA is transformed into a translation activation signal, recruiting Argonaute (AGO) and fragile X mental retardation-related protein 1 (FXR1), factors associated with micro-ribonucleoproteins (microRNPs). We show that human microRNA miR369-3 directs association of these proteins with the AREs to activate translation. Furthermore, we document that two well-studied microRNAs-Let-7 and the synthetic microRNA miRcxcr4-likewise induce translation up-regulation of target mRNAs on cell cycle arrest, yet they repress translation in proliferating cells. Thus, activation is a common function of microRNPs on cell cycle arrest. We propose that translation regulation by microRNPs oscillates between repression and activation during the cell cycle.
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              Colorectal cancer epidemiology: incidence, mortality, survival, and risk factors.

              In this article, the incidence, mortality, and survival rates for colorectal cancer are reviewed, with attention paid to regional variations and changes over time. A concise overview of known risk factors associated with colorectal cancer is provided, including familial and hereditary factors, as well as environmental lifestyle-related risk factors such as physical inactivity, obesity, smoking, and alcohol consumption.
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                Author and article information

                Journal
                Oncol Rep
                Oncol. Rep
                Oncology Reports
                D.A. Spandidos
                1021-335X
                1791-2431
                June 2018
                21 March 2018
                21 March 2018
                : 39
                : 6
                : 2455-2472
                Affiliations
                [1 ]Laboratory of Anatomy-Histology-Embryology, Medical School, University of Crete, 71110 Heraklion, Greece
                [2 ]Laboratory of Forensic Sciences and Toxicology, Medical School, University of Crete, 71409 Heraklion, Crete, Greece
                [3 ]Laboratory of Anatomy and Histology, Nursing School, National and Kapodistrian University of Athens, 11527 Athens, Greece
                [4 ]Foundation for Research and Technology Hellas (FORTH), Institute of Computer Sciences (ICS), Computational Biomedicine Laboratory (CBML), 71003 Heraklion, Crete, Greece
                [5 ]Laboratory of Clinical Virology, Medical School, University of Crete, 71003 Heraklion, Crete, Greece
                Author notes
                Correspondence to: Professor Aristides M. Tsatsakis, Laboratory of Forensic Sciences and Toxicology, Medical School, University of Crete, Voutes, 71409 Heraklion, Crete, Greece, E-mail: toxlab.uoc@ 123456gmail.com
                Article
                or-39-06-2455
                10.3892/or.2018.6330
                5983921
                29565457
                298656c3-ebe3-4593-862c-42ba1cbf0e94
                Copyright: © Nikolouzakis et al.

                This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

                History
                : 01 February 2018
                : 21 March 2018
                Categories
                Review

                colorectal cancer,diagnosis,prognosis,prediction,biomarkers,dna markers,non-dna markers

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