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      OncoTargets and Therapy (submit here)

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      Holliday junction–recognizing protein promotes cell proliferation and correlates with unfavorable clinical outcome of hepatocellular carcinoma

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          Abstract

          Aim

          To investigate the expression and clinical significance of Holliday junction–recognizing protein (HJURP) in hepatocellular carcinoma (HCC).

          Methods

          In this study, we detected the expression of HJURP protein in samples of 164 patients with HCC, and based on this, we divided the patients into two cohorts: high expression of HJURP and low expression of HJURP. We analyzed the correlation between HJURP expression and the clinicopathological factors using chi-square test. Survival significance of HJURP was defined by Kaplan–Meier method and log-rank test, and the independent prognostic factors were identified by Cox regression model. Using function assays of HCC cell lines, we investigated the influence of HJURP on the proliferation of HCC cells.

          Results

          In our study, the proportion of patients with high HJURP expression was 25.6%, which was significantly associated with the tumor size and Barcelona clinic liver cancer stage. Univariate analysis confirmed that high HJURP expression was remarkably associated with poorer overall survival rates ( P=0.003), as well as tumor number ( P=0.016), tumor differentiation ( P=0.047), TNM stage ( P=0.005), and Barcelona clinic liver cancer stage ( P=0.004). Multivariate analysis confirmed that high HJURP expression ( P<0.001) acted as an independent prognostic risk factor of unfavorable prognosis. Real-time polymerase chain reaction analysis revealed that the expression of HJURP was significantly higher in HCC tissues than that in the corresponding normal liver tissues. Moreover, we demonstrated that HJURP overexpression could accelerate HCC cell line proliferation, whereas HJURP knockdown could attenuate the proliferation.

          Conclusion

          High HJURP expression was an independent prognostic biomarker of HCC, predicting poorer prognosis. HJURP also played an important role in HCC cell proliferation.

          Most cited references16

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          Management of hepatocellular carcinoma.

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            Genetic variants in STAT4 and HLA-DQ genes confer risk of hepatitis B virus-related hepatocellular carcinoma.

            To identify genetic susceptibility loci for hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) in the Chinese population, we carried out a genome-wide association study (GWAS) in 2,514 chronic HBV carriers (1,161 HCC cases and 1,353 controls) followed by a 2-stage validation among 6 independent populations of chronic HBV carriers (4,319 cases and 4,966 controls). The joint analyses showed that HCC risk was significantly associated with two independent loci: rs7574865 at STAT4, P(meta) = 2.48 × 10(-10), odds ratio (OR) = 1.21; and rs9275319 at HLA-DQ, P(meta) = 2.72 × 10(-17), OR = 1.49. The risk allele G at rs7574865 was significantly associated with lower mRNA levels of STAT4 in both the HCC tissues and nontumor tissues of 155 individuals with HBV-related HCC (P(trend) = 0.0008 and 0.0002, respectively). We also found significantly lower mRNA expression of STAT4 in HCC tumor tissues compared with paired adjacent nontumor tissues (P = 2.33 × 10(-14)).
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              Staging of hepatocellular carcinoma: assessment of the Japanese TNM and AJCC/UICC TNM systems in a cohort of 13,772 patients in Japan.

              The aims of this study were to present evidence to develop and validate the Japanese Tumor-Node-Metastasis (TNM) staging system for primary liver cancer and to compare its discriminatory ability and predictive power with those of Vauthey's simplified staging, which was adopted as the TNM staging system of the American Joint Committee on Cancer (AJCC)/International Union Against Cancer (UICC). Among many staging systems for hepatocellular carcinoma, the Japanese TNM staging system and the AJCC/UICC staging system were developed based on a survival analysis of surgical patients. These 2 staging systems have not been compared in large series. The Liver Cancer Study Group of Japan (LCSGJ) prospectively collected clinicopathologic data of 63,736 patients with primary liver cancer from 1995 to 2001. Among them, 13,772 patients received curative hepatic resection. Based on univariate and multivariate survival analyses, the Japanese TNM staging system was developed. The accuracy of the Japanese TNM staging system for predicting patient survival was compared with that of the AJCC/UICC staging system using the cross-validation method. The independent prognostic factors (relative risk; 95% confidence interval) were vascular or bile duct invasion (1.36;1.29-1.43), liver cirrhosis (1.26;1.20-1.32), diameter ( 2 cm) (1.21;1.14-1.28), alpha-fetoprotein (1.20;1.15-1.25), single/multiple (1.18;1.12-1.23), liver damage (1.15;1.10-1.20), hepatic involvement (1.14;1.09-1.19), histologic differentiation (1.14;1.08-1.20), gross classification (1.13;1.08-1.18), and esophageal varices (1.07;1.02-1.13). Based on these results, 3 criteria (vascular or bile duct invasion, diameter, and single/multiple) were selected. Patients with none of these 3 factors were considered T1, and those with 1, 2, and 3 factors were T2, T3, and T4, respectively. The number of patients and 5-year survival rates for T1, T2, T3, and T4 were 2078, 70%; 6853, 58%; 3021, 41%; and 582, 24% (P < 0.0001), respectively, while those for the AJCC-T were 8457, 61% in T1, 2888, 46% in T2, and 1189, 30% in T3 (P < 0.0001). While both the LCSGJ-T and the AJCC-T had good discriminating ability, the former was significantly superior (P = 0.0007). Our findings support the development of LCSG stage. While both staging systems allow for the clear stratification of patients into prognostic groups, the LCSGJ staging may be more appropriate for stratifying patients with early-stage HCC.
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                Author and article information

                Journal
                Onco Targets Ther
                Onco Targets Ther
                OncoTargets and Therapy
                OncoTargets and therapy
                Dove Medical Press
                1178-6930
                2017
                17 May 2017
                : 10
                : 2601-2607
                Affiliations
                [1 ]Department of Health Care Oncology, East District of Shandong Provincial Hospital of Shandong University, Jinan
                [2 ]Department of Medical Oncology
                [3 ]Department of Intensive Care Unit, Yantai Yuhuangding Hospital Affiliated to Qingdao University, Yantai, Shandong
                [4 ]Department of Geriatrics, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, People’s Republic of China
                Author notes
                Correspondence: Peng Li, Department of Medical Oncology, Yantai Yuhuangding Hospital Affiliated to Qingdao University, 20 Yuhuangdingdong Road, Yantai, Shandong 264000, People’s Republic of China, Fax +86 535 624 0341, Email lipengyuhuangding@ 123456163.com
                Mingyong Han, East District of Shandong Provincial Hospital of Shandong University, 9677 Aotizhong Road, Jinan, Shandong 250021, People’s Republic of China, Fax +86 531 8793 8911, Email hanmy0531@ 123456163.com
                [*]

                These authors contributed equally to this work

                Article
                ott-10-2601
                10.2147/OTT.S127738
                5440066
                28553125
                a9915108-7de3-4269-bf2c-27e59a94166f
                © 2017 Hu et al. This work is published and licensed by Dove Medical Press Limited

                The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

                History
                Categories
                Original Research

                Oncology & Radiotherapy
                holliday junction-recognizing protein,hepatocellular carcinoma,proliferation,prognosis

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