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      Low expression of RecQ-like helicase 5 is associated with poor prognosis in patients with gastric cancer

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          Abstract

          The role of RecQ-like helicase 5 (RECQL5) in gastric cancer (GC) is unclear. This study investigated the expression, clinicopathological association and prognosis of RECQL5 protein in human GC. Firstly, the Oncomine database was used to determine the mRNA expression levels of RECQL5 in GC samples. GC samples and adjacent normal gastric tissue samples were subsequently assessed to determine RECQL5 protein expression levels using immunohistochemistry. The clinicopathological association with RECQL5 expression was analyzed. Multivariate Cox analysis was performed to determine the relationship between RECQL5 expression and survival outcomes. Data from the Oncomine database revealed that RECQL5 mRNA was significantly downregulated in GC tissues compared with that in normal gastric tissues (P<0.05). These results were then validated at the protein level as RECQL5 protein expression was found to be significantly downregulated in GC samples compared with that in normal gastric tissues (P<0.05). Low expression of RECQL5 was significantly associated with depth of tumor invasion, histological differentiation and TNM stage (all P<0.05) and indicated poor prognosis in patients with GC. Multivariate analysis revealed that low RECQL5 expression and depth of invasion were independent prognostic factors for GC (P<0.05). These results suggest that low expression of RECQL5 is associated with carcinogenesis and invasion in GC and with poor overall survival in patients with GC. RECQL5 may be a novel prognostic marker for patients with GC.

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          Most cited references26

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          Genome-wide expression profile of sporadic gastric cancers with microsatellite instability.

          Gastric cancers with mismatch repair (MMR) inactivation are characterised by microsatellite instability (MSI). In this study, the transcriptional profile of 38 gastric cancers with and without MSI was analysed. Unsupervised analysis showed that the immune and apoptotic gene networks efficiently discriminated these two cancer types. Hierarchical clustering analysis revealed numerous gene expression changes associated with the MSI phenotype. Amongst these, the p53-responsive genes maspin and 14-3-3 sigma were significantly more expressed in tumours with than without MSI. A tight immunosurveillance coupled with a functional p53 gene response is consistent with the better prognosis of MSI cancers. Frequent silencing of MLH1 and downregulation of MMR target genes, such as MRE11 and MBD4, characterised MSI tumours. The downregulation of SMUG1 was also a typical feature of these tumours. The DNA repair gene expression profile of gastric cancer with MSI is of relevance for therapy response.
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            Changing Trends in Stomach Cancer Throughout the World.

            The paper aims to discuss the global trends in gastric cancer incidence in relation to important factors involved in the pathogenesis of gastric cancer.
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              The RecQ DNA helicases in DNA repair.

              The RecQ helicases are conserved from bacteria to humans and play a critical role in genome stability. In humans, loss of RecQ gene function is associated with cancer predisposition and/or premature aging. Recent experiments have shown that the RecQ helicases function during distinct steps during DNA repair; DNA end resection, displacement-loop (D-loop) processing, branch migration, and resolution of double Holliday junctions (dHJs). RecQ function in these different processing steps has important implications for its role in repair of double-strand breaks (DSBs) that occur during DNA replication and meiosis, as well as at specific genomic loci such as telomeres.
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                Author and article information

                Journal
                Oncol Lett
                Oncol Lett
                OL
                Oncology Letters
                D.A. Spandidos
                1792-1074
                1792-1082
                January 2020
                21 November 2019
                21 November 2019
                : 19
                : 1
                : 985-991
                Affiliations
                [1 ]Department of Gastrointestinal Surgery, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510655, P.R. China
                [2 ]Department of Digestion, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510655, P.R. China
                [3 ]Gastrointestinal Endoscopy Center, The Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong 518033, P.R. China
                Author notes
                Correspondence to: Professor Junsheng Peng, Department of Gastrointestinal Surgery, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, 26 Yuancun Er Heng Road, Tianhe, Guangzhou, Guangdong 510655, P.R. China, E-mail: pengsir1010@ 123456126.com
                Professor Honglei Chen, Gastrointestinal Endoscopy Center, The Eighth Affiliated Hospital, Sun Yat-sen University, No. 3025 Shennan Zhong Road, Futian, Shenzhen, Guangdong 518033, P.R. China, E-mail: chl_830830@ 123456163.com
                [*]

                Contributed equally

                Article
                OL-0-0-11137
                10.3892/ol.2019.11137
                6924161
                df697593-633c-48a1-a2f2-1ede0581eb18
                Copyright: © Lin et al.

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, reproduction and adaptation in any medium and for any purpose provided that it is properly attributed. For attribution, the original author(s), title, publication source (PeerJ) and either DOI or URL of the article must be cited.

                History
                : 09 June 2019
                : 25 October 2019
                Categories
                Articles

                Oncology & Radiotherapy
                recq-like helicase 5,gastric cancer,immunohistochemistry,prognosis
                Oncology & Radiotherapy
                recq-like helicase 5, gastric cancer, immunohistochemistry, prognosis

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