Roles of diencephalon/mesencephalon homeobox 1 in the development and prognosis of hepatocellular carcinoma

Introduction and objectives: The oncogene diencephalon/mesencephalon homeobox 1 (DMBX1) is widely overexpressed in a variety of human cancers. The present study aimed to analyze the expression and clinical importance of DMBX1 in nonneoplastic tissues and tumor tissues from patients with hepatocellul...

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Main Authors: Xiaoting Huang, Leyang Xiang, Wei Liu, Mingyi Li, Anbang Ren, Zide Chen, Chu Zheng, Chen Chengcong, Jinquan Liu, Yawei Yuan
Format: Article
Language:English
Published: Elsevier 2021-09-01
Series:Annals of Hepatology
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S1665268121000132
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author Xiaoting Huang
Leyang Xiang
Wei Liu
Mingyi Li
Anbang Ren
Zide Chen
Chu Zheng
Chen Chengcong
Jinquan Liu
Yawei Yuan
author_facet Xiaoting Huang
Leyang Xiang
Wei Liu
Mingyi Li
Anbang Ren
Zide Chen
Chu Zheng
Chen Chengcong
Jinquan Liu
Yawei Yuan
author_sort Xiaoting Huang
collection DOAJ
description Introduction and objectives: The oncogene diencephalon/mesencephalon homeobox 1 (DMBX1) is widely overexpressed in a variety of human cancers. The present study aimed to analyze the expression and clinical importance of DMBX1 in nonneoplastic tissues and tumor tissues from patients with hepatocellular carcinoma (HCC). Materials and methods: DMBX1 expression in HCC and adjacent nontumor tissues was analyzed using immunohistochemical staining. Chi-square tests were applied to compare DMBX1 expression between the tumors and the adjacent normal tissues. We explored the correlation of DMBX1 expression with clinicopathological factors and its effect on the prognosis of HCC. Finally, we investigated the role of DMBX1 in HCC via knockdown experiments, which analyzed changes in cell invasion, cell proliferation and epithelial-mesenchymal transition (EMT) biomarkers (E-cadherin, N-cadherin, vimentin). The mRNAs that were coexpressed with DMBX1 in HCC, based on the TCGA cohort (n = 366), were obtained from the cBioPortal database. Results: The average score for DMBX1 expression was significantly different (P < 0.001) between HCC and paired adjacent nontumor tissues, and DMBX1 expression correlated with hepatitis B virus (HBV) infection, tumor size, metastasis, and tumor node metastasis (TNM) stage (P < 0.05). A multivariate Cox regression analysis identified significant correlations of DMBX1 expression with tumor metastasis, TNM stage, and tumor capsule. Moreover, Kaplan-Meier survival analysis revealed an association between DMBX1 overexpression and shorter overall survival of patients with HCC (P < 0.05). In HCC cell lines, silencing DMBX1 markedly inhibited migration, proliferation and EMT markers. The mRNAs that were negatively (R ≤ −0.25, n = 1094) or positively (R ≥ 0.25, n = 2906) coexpressed with DMBX1 mRNA were selected for further Gene Ontology enrichment analysis, and the results revealed that the predicted functions of DMBX1 in HCC support the in vitro experimental results. Conclusions: Our data provide evidence that DMBX1 overexpression is associated with HCC metastasis and poor prognosis, suggesting that DMBX1 represents a therapeutic target in HCC.
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spelling doaj.art-46de6108aedf43aba1f74a2d6504f72f2022-12-21T18:46:33ZengElsevierAnnals of Hepatology1665-26812021-09-0124100314Roles of diencephalon/mesencephalon homeobox 1 in the development and prognosis of hepatocellular carcinomaXiaoting Huang0Leyang Xiang1Wei Liu2Mingyi Li3Anbang Ren4Zide Chen5Chu Zheng6Chen Chengcong7Jinquan Liu8Yawei Yuan9Department of Radiation Oncology, Affiliated Cancer Hospital &amp; Institute of Guangzhou Medical University, Guangzhou, China; State Key Laboratory of Respiratory Diseases, Guangzhou Institute of Respiratory Disease, Affiliated Cancer Hospital &amp; Institute of Guangzhou Medical University, Guangzhou, ChinaDepartment of Surgery, Affiliated Cancer Hospital &amp; Institute of Guangzhou Medical University, Guangzhou, ChinaDepartment of Radiation Oncology, Affiliated Cancer Hospital &amp; Institute of Guangzhou Medical University, Guangzhou, China; State Key Laboratory of Respiratory Diseases, Guangzhou Institute of Respiratory Disease, Affiliated Cancer Hospital &amp; Institute of Guangzhou Medical University, Guangzhou, ChinaDepartment of Radiation Oncology, Affiliated Cancer Hospital &amp; Institute of Guangzhou Medical University, Guangzhou, China; State Key Laboratory of Respiratory Diseases, Guangzhou Institute of Respiratory Disease, Affiliated Cancer Hospital &amp; Institute of Guangzhou Medical University, Guangzhou, ChinaDepartment of Radiation Oncology, Affiliated Cancer Hospital &amp; Institute of Guangzhou Medical University, Guangzhou, China; State Key Laboratory of Respiratory Diseases, Guangzhou Institute of Respiratory Disease, Affiliated Cancer Hospital &amp; Institute of Guangzhou Medical University, Guangzhou, ChinaDepartment of Radiation Oncology, The 2nd Clinical Medical College (Shenzhen People’s Hospital) of Jinan University, Shenzhen, ChinaAcademic Office, Guilin Medical University, Guilin, ChinaDepartment of Radiation Oncology, Affiliated Cancer Hospital &amp; Institute of Guangzhou Medical University, Guangzhou, China; State Key Laboratory of Respiratory Diseases, Guangzhou Institute of Respiratory Disease, Affiliated Cancer Hospital &amp; Institute of Guangzhou Medical University, Guangzhou, ChinaDepartment of Radiation Oncology, Affiliated Cancer Hospital &amp; Institute of Guangzhou Medical University, Guangzhou, China; State Key Laboratory of Respiratory Diseases, Guangzhou Institute of Respiratory Disease, Affiliated Cancer Hospital &amp; Institute of Guangzhou Medical University, Guangzhou, China; Corresponding authors at: Department of Radiation Oncology, Affiliated Cancer Hospital &amp; Institute of Guangzhou Medical University, No 78, Hengzhigang Road, Yuexiu District, Guangzhou, Guangdong 510095, People’s Republic of China.Department of Radiation Oncology, Affiliated Cancer Hospital &amp; Institute of Guangzhou Medical University, Guangzhou, China; State Key Laboratory of Respiratory Diseases, Guangzhou Institute of Respiratory Disease, Affiliated Cancer Hospital &amp; Institute of Guangzhou Medical University, Guangzhou, China; Corresponding authors at: Department of Radiation Oncology, Affiliated Cancer Hospital &amp; Institute of Guangzhou Medical University, No 78, Hengzhigang Road, Yuexiu District, Guangzhou, Guangdong 510095, People’s Republic of China.Introduction and objectives: The oncogene diencephalon/mesencephalon homeobox 1 (DMBX1) is widely overexpressed in a variety of human cancers. The present study aimed to analyze the expression and clinical importance of DMBX1 in nonneoplastic tissues and tumor tissues from patients with hepatocellular carcinoma (HCC). Materials and methods: DMBX1 expression in HCC and adjacent nontumor tissues was analyzed using immunohistochemical staining. Chi-square tests were applied to compare DMBX1 expression between the tumors and the adjacent normal tissues. We explored the correlation of DMBX1 expression with clinicopathological factors and its effect on the prognosis of HCC. Finally, we investigated the role of DMBX1 in HCC via knockdown experiments, which analyzed changes in cell invasion, cell proliferation and epithelial-mesenchymal transition (EMT) biomarkers (E-cadherin, N-cadherin, vimentin). The mRNAs that were coexpressed with DMBX1 in HCC, based on the TCGA cohort (n = 366), were obtained from the cBioPortal database. Results: The average score for DMBX1 expression was significantly different (P < 0.001) between HCC and paired adjacent nontumor tissues, and DMBX1 expression correlated with hepatitis B virus (HBV) infection, tumor size, metastasis, and tumor node metastasis (TNM) stage (P < 0.05). A multivariate Cox regression analysis identified significant correlations of DMBX1 expression with tumor metastasis, TNM stage, and tumor capsule. Moreover, Kaplan-Meier survival analysis revealed an association between DMBX1 overexpression and shorter overall survival of patients with HCC (P < 0.05). In HCC cell lines, silencing DMBX1 markedly inhibited migration, proliferation and EMT markers. The mRNAs that were negatively (R ≤ −0.25, n = 1094) or positively (R ≥ 0.25, n = 2906) coexpressed with DMBX1 mRNA were selected for further Gene Ontology enrichment analysis, and the results revealed that the predicted functions of DMBX1 in HCC support the in vitro experimental results. Conclusions: Our data provide evidence that DMBX1 overexpression is associated with HCC metastasis and poor prognosis, suggesting that DMBX1 represents a therapeutic target in HCC.http://www.sciencedirect.com/science/article/pii/S1665268121000132DMBX1HCCPrognosisProliferationMetastasis
spellingShingle Xiaoting Huang
Leyang Xiang
Wei Liu
Mingyi Li
Anbang Ren
Zide Chen
Chu Zheng
Chen Chengcong
Jinquan Liu
Yawei Yuan
Roles of diencephalon/mesencephalon homeobox 1 in the development and prognosis of hepatocellular carcinoma
Annals of Hepatology
DMBX1
HCC
Prognosis
Proliferation
Metastasis
title Roles of diencephalon/mesencephalon homeobox 1 in the development and prognosis of hepatocellular carcinoma
title_full Roles of diencephalon/mesencephalon homeobox 1 in the development and prognosis of hepatocellular carcinoma
title_fullStr Roles of diencephalon/mesencephalon homeobox 1 in the development and prognosis of hepatocellular carcinoma
title_full_unstemmed Roles of diencephalon/mesencephalon homeobox 1 in the development and prognosis of hepatocellular carcinoma
title_short Roles of diencephalon/mesencephalon homeobox 1 in the development and prognosis of hepatocellular carcinoma
title_sort roles of diencephalon mesencephalon homeobox 1 in the development and prognosis of hepatocellular carcinoma
topic DMBX1
HCC
Prognosis
Proliferation
Metastasis
url http://www.sciencedirect.com/science/article/pii/S1665268121000132
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