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      The Upregulation of Trophinin-Associated Protein (TROAP) Predicts a Poor Prognosis in Hepatocellular Carcinoma

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          Abstract

          Purpose: Trophinin-associated protein (TROAP) is a cytoplasmic protein that plays a significant role in the processes of embryo transplantation and microtubule regulation. However, the relevant survival analysis and cancer progression analysis have not yet been reported.

          Methods: Eighteen matched pairs of tumor and adjacent non-tumor samples were evaluated to detect the TROAP mRNA level. Immunohistochemistry (IHC) was used to evaluate the TROAP expression in 108 hepatocellular carcinoma patients who underwent surgical resection. Meanwhile, data from the TCGA database was statistically evaluated.

          Results: In the present study, we detected a significant increase in the TROAP mRNA level in tumor tissues when compared with adjacent non-tumor tissues. Moreover, the upregulation of TROAP was associated with increased serum AFP and GGT; the greater the tumor number was, the larger the tumor size, differentiation grade, and cancer embolus in clinical analysis. In HCC patients, elevated TROAP expression in the primary tumor was positively related to clinical severity, such as poor overall survival and disease-free survival. In addition, both univariate and multivariate survival analysis validated that TROAP expression was a promising independent risk factor for overall survival and disease-free survival in HCC patients. Furthermore, the results derived from the analysis of data from the TCGA database were consistent with previous results. Altogether, our results show that TROAP is a novel crucial regulator of HCC progression and is a potential therapeutic biomarker for HCC patients.

          Conclusions: Elevated TROAP expression predicted a poor prognosis, and TROAP may serve as a potential biomarker for application in oncotherapy.

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          Most cited references31

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          Diagnostic and prognostic role of alpha-fetoprotein in hepatocellular carcinoma: both or neither?

          The clinical usefulness of alpha-fetoprotein (AFP) in hepatocellular carcinoma (HCC) management is debatable. To assess, in a large multi-centric survey, diagnostic and prognostic reliability of AFP, predictive factors, and any correlation with the tumor immunophenotype. A total of 1,158 patients with HCC were analyzed with reference to serum AFP levels at diagnosis. We evaluated: HCC grading, histotype, and size; Okuda, tumor-nodes-metastases (TNM), and Child-Pugh scores; liver function, symptoms, presence of metastases or portal thrombosis, etiology, survival, and treatment. In 66 patients with histological diagnosis, the pathologists evaluated p53 overexpression, MIB 1 labeling index, BCL-2 positive cells (index of apoptosis), and CD44 (adhesion molecule) positivity. Patients were divided into three AFP groups: normal ( 400 ng/mL) [18%]. Statistical correlations were significant for: weight loss (p= 0.0056), pain (p= 0.0025), Child-Pugh score (p= 0.001), tumor size, Okuda's and TNM stages, metastases, thrombosis, type of treatment (all p < 0.0001), and female sex (p < 0.004). AFP correlated with survival overall, in patients untreated, transplanted, or undergoing locoregional treatments; but not in those surgically treated. In the discriminant analysis, the related variables were size, female sex, Child-Pugh score, TNM staging (steps 1-4). When using the receiver operating characteristic curve, the prognostic reliability of AFP was limited with area under the curve of 0.59. Finally, patients with low expression of BCL2 had high AFP levels (p < 0.05). AFP positively correlated with Edmonson score (p < 0.0001). The evaluation of this large series of HCC patients allowed us to: confirm the low sensitivity (54%) of AFP in the diagnosis of HCC and its prognostic value, albeit limited, being tumor size, female sex (intriguingly enough), Child-Pugh score, and TNM staging independent predictors.
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            NCCN clinical practice guidelines in oncology: hepatobiliary cancers.

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              Major achievements in hepatocellular carcinoma.

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                Author and article information

                Journal
                J Cancer
                J Cancer
                jca
                Journal of Cancer
                Ivyspring International Publisher (Sydney )
                1837-9664
                2019
                29 January 2019
                : 10
                : 4
                : 957-967
                Affiliations
                [1 ]Department of Chinese Medicine, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, Guangdong, P. R. China
                [2 ]State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou 510060, P. R. China
                [3 ]Department of Chinese Medicine, the Third Affiliated Hospital, Sun Yat-sen University, Guangzhou 510630, Guangdong, P. R. China.
                Author notes
                ✉ Corresponding authors: Bi-Jun Huang, State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou 510060, P. R. China. Email: huangbj@ 123456sysucc.org.cn . Dr. Shi-Jun Zhang, Department of Chinese Medicine, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, Guangdong, P. R. China; Email: zhsjun1967@ 123456hotmail.com .

                * The first two authors contributed to the study equally

                Competing Interests: The authors have declared that no competing interest exists.

                Article
                jcav10p0957
                10.7150/jca.26666
                6400818
                30854102
                7af2d6ae-7a92-4351-96e0-f76e2c59a831
                © Ivyspring International Publisher

                This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license ( https://creativecommons.org/licenses/by-nc/4.0/). See http://ivyspring.com/terms for full terms and conditions.

                History
                : 13 April 2018
                : 4 January 2019
                Categories
                Research Paper

                Oncology & Radiotherapy
                trophinin-associated protein,hepatocellular carcinoma,prognosis,and biomarker.

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