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      Inflammatory Markers and MicroRNAs: The Backstage Actors Influencing Prognosis in Colorectal Cancer Patients

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          Abstract

          Background: Colorectal cancer (CRC) remains a deadly disease, afflicting the lives of millions worldwide. The prognosis of CRC patients is best predicted by surgical resection and pathological analysis of specimens. Emerging evidence has attributed a significant role to inflammatory markers and microRNAs (miRNAs) in the prognosis and survival of CRC patients. Aim: Here, we review the literature on inflammatory markers and miRNAs with an established role on survival rates, response to systemic chemotherapy, and other clinic-pathological parameters in CRC patients. Results: Our literature review revealed a critical role of inflammatory markers—specifically, the acute-phase proteins, inflammatory cytokines, and blood cell ratios—on prognostic outcomes in CRC patients. MiRNAs, on the other hand, were useful in predicting prognosis and clinical response and accordingly stratifying CRC patients for optimal drug selection. Conclusion: These biomarkers are easily measured in routine blood exams and can be used in adjunct to the tumor-node-metastasis (TNM) staging system to identify high-risk patients and those who are more likely to benefit from chemotherapy and other targeted therapies. However, more prospective studies are needed for the validation of these discussed prognostic and predictive biomarkers.

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          Exosomal microRNA in serum is a novel biomarker of recurrence in human colorectal cancer

          Background: Functional microRNAs (miRNAs) in exosomes have been recognised as potential stable biomarkers in cancers. The aim of this study is to identify specific miRNAs in exosome as serum biomarkers for the early detection of recurrence in human colorectal cancer (CRC). Methods: Serum samples were sequentially obtained from six patients with and without recurrent CRC. The miRNAs were purified from exosomes, and miRNA microarray analysis was performed. The miRNA expression profiles and copy number aberrations were explored using microarray and array CGH analyses in 124 CRC tissues. Then, we validated exosomal miRNAs in 2 serum sample sets (90 and 209 CRC patients) by quantitative real-time RT–PCR. Results: Exosomal miR-17-92a cluster expression level in serum was correlated with the recurrence of CRC. Exosomal miR-19a expression levels in serum were significantly increased in patients with CRC as compared with healthy individuals with gene amplification. The CRC patients with high exosomal miR-19a expression showed poorer prognoses than the low expression group (P<0.001). Conclusions: Abundant expression of exosomal miR-19a in serum was identified as a prognostic biomarker for recurrence in CRC patients.
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            The Lymphocyte-to-Monocyte Ratio is a Superior Predictor of Overall Survival in Comparison to Established Biomarkers of Resectable Colorectal Cancer

            Objective: The study aims to investigate the prognostic value of the lymphocyte-to-monocyte ratio (LMR) in patients with colorectal cancer (CRC) undergoing curative resection and to compare it to established biomarkers including the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), modified Glasgow prognostic score (mGPS), and combined BRAF-mismatch repair (MMR) status. Background: The prognostic significance of systemic inflammatory markers in CRC such as the NLR, PLR, and mGPS has been well defined. Commonly used genetic markers such as combined BRAF-MMR status have also been found to be prognostic. Recent evidence, although limited, suggests that the preoperative LMR may be prognostic in CRC. Methods: Data from the Northern Sydney Local Health District from January 1998 to December 2012 were retrospectively collected. Of 3281 consecutive patients identified, 1623 patients who underwent curative resection were deemed eligible for inclusion. The relation between the LMR, clinicopathologic variables, and other biomarkers were analyzed in Kaplan-Meier log-rank survival analysis and then multivariate Cox regression models looking for association with overall survival (OS). Results: In multivariate analysis of all patients, elevated LMR was associated with better OS (hazard ratio 0.569, 95% confidence interval: 0.478–0.677, P < 0.001) independent of age (P < 0.001), T stage (P < 0.001), N stage (P < 0.001), and grade (P = 0.049). The NLR, PLR, and combined BRAF-MMR status were not independently significant. In multivariate subgroup analysis of 389 patients with mGPS, LMR remained the only independently significant biomarker (hazard ratio 0.620, 95% confidence interval: 0.437–0.880, P = 0.007). Conclusions: The LMR is an independent predictor of OS in patients with CRC undergoing curative resection and appears to be superior to pre-existing biomarkers.
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              Clinical Significance of the C-Reactive Protein to Albumin Ratio for Survival After Surgery for Colorectal Cancer.

              This study was designed to estimate the clinical significance of the C-reactive protein (CRP)/albumin ratio (CAR) for prediction of postoperative survival in patients with colorectal cancer (CRC).
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                Author and article information

                Journal
                Int J Mol Sci
                Int J Mol Sci
                ijms
                International Journal of Molecular Sciences
                MDPI
                1422-0067
                26 June 2018
                July 2018
                : 19
                : 7
                : 1867
                Affiliations
                Department of Internal Medicine, American University of Beirut Medical Center, Riad El Solh, Beirut 110 72020, Lebanon; rn03@ 123456aub.edu.lb (R.N.); ms302@ 123456aub.edu.lb (M.S.H.); fn17@ 123456aub.edu.lb (F.N.); dm25@ 123456aub.edu.lb (D.M.); as04@ 123456aub.edu.lb (A.S.)
                Author notes
                [* ]Correspondence: st29@ 123456aub.edu.lb ; Tel.: +961-1-374374
                [†]

                These authors contributed equally to this work.

                Article
                ijms-19-01867
                10.3390/ijms19071867
                6073730
                29949857
                f1238376-65e6-47b4-afaf-ae81ddb270ba
                © 2018 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 31 May 2018
                : 25 June 2018
                Categories
                Review

                Molecular biology
                colorectal cancer,microrna,inflammatory markers,prognosis,survival outcomes
                Molecular biology
                colorectal cancer, microrna, inflammatory markers, prognosis, survival outcomes

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