Expression and Prognostic Significance of Golgiglycoprotein73 (GP73) with Epithelial-mesenchymal Transition (EMT) Related Molecules in Hepatocellular Carcinoma (HCC)

Overview

Journal Diagn Pathol

Publisher Biomed Central

Specialty Pathology

Date 2013 Dec 10

PMID 24313979

Citations 26

Authors

Yong Xing Bao

Qian Cao

Ying Yang

Rui Mao

Lei Xiao

Hua Zhang

Hua-Rong Zhao

Hao Wen

Affiliations

Soon will be listed here.

Abstract

Background: Hepatocellular carcinoma (HCC) is the fifth most common cancer and the third cause of cancer-related deaths, worldwide. It is essential to develop an effective prognostic biomarker and determine the mechanisms underlying HCC invasion and metastasis.

Aims: This study aimed to investigate the expression of Golgi glycoprotein73 (GP73) and Epithelial-mesenchymal transition (EMT) molecules such as E-cadherin and Vimentin in HCC. We also evaluated the prognostic value of GP73 in HCC.

Methods: Immunohistochemistry (IHC) was used to determine the expression of GP73 and EMT molecules in 75 HCC specimens and the corresponding paracarcinomatous liver (PCL) tissues. Spearman's correlation test was used to analyze the correlation of GP73 and EMT molecules. Clinicopathological features of the HCC patients were also analyzed. Univariate survival analysis was performed by the Kaplan-Meier method and differences among the groups were analyzed by the Log-rank test.

Results: GP73 expression in HCC was higher compared with PCL tissues (χ2 = 73.60, P < 0.05). EMT molecules were also detected in HCC and PCL tissues. GP73 was negatively correlated with E-cadherin (r = - 0.49, P < 0.05), but positively correlated with Vimentin (r = 0.46, P < 0.05) in HCC. GP73 was correlated with the clinicopathological features including Edmondson grade, vascular invasion and TNM stage (P < 0.05), which was also associated with overall survival (OS) (P < 0.05).

Conclusions: GP73 was negatively with E-cadherin and positively correlated with Vimentin. It might be associated with aggressive behavior of HCC and had influence on patients' OS. Further research is needed to determine the potential of GP73.

Virtual Slides: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/29 vs/1504046946108618; http://med.motic.com/MoticGallery/Slide?id=3b6a037e-f60e-4c68-9106-41e790de9431&user=2C69F0D6-A478-4A2B-ABF0-BB36763E8025; http://med.motic.com/MoticGallery/Slide?id=a25b5b32-b613-47b0-9f8b-e1e67a95d1bf&user=2C69F0D6-A478-4A2B-ABF0-BB36763E8025.

Citing Articles

A meta-analysis of the prognostic impact of tissue golgi protein 73 (tGP73) in hepatocellular carcinoma.

Yu W, Li G, Lou M, Wu Z BMC Gastroenterol. 2023; 23(1):401.

PMID: 37978447 PMC: 10656938. DOI: 10.1186/s12876-023-03050-5.

Golgi Apparatus Target Proteins in Gastroenterological Cancers: A Comprehensive Review of GOLPH3 and GOLGA Proteins.

Bucurica S, Gaman L, Jinga M, Popa A, Ionita-Radu F Cells. 2023; 12(14).

PMID: 37508488 PMC: 10378073. DOI: 10.3390/cells12141823.

Liang X, Yin Y, Li N Front Genet. 2022; 13:1051168.

PMID: 36468024 PMC: 9716024. DOI: 10.3389/fgene.2022.1051168.

The Single-Cell Level Perspective of the Tumor Microenvironment and Its Remodeling by CAR-T Cells.

Gao S, Sugimura R Cancer Treat Res. 2022; 183:275-285.

PMID: 35551664 DOI: 10.1007/978-3-030-96376-7_10.

Golgi Phosphoprotein 73: The Driver of Epithelial-Mesenchymal Transition in Cancer.

Liu Y, Hu X, Liu S, Zhou S, Chen Z, Jin H Front Oncol. 2021; 11:783860.

PMID: 34950590 PMC: 8688837. DOI: 10.3389/fonc.2021.783860.

References

Mima K, Okabe H, Ishimoto T, Hayashi H, Nakagawa S, Kuroki H . CD44s regulates the TGF-β-mediated mesenchymal phenotype and is associated with poor prognosis in patients with hepatocellular carcinoma. Cancer Res. 2012; 72(13):3414-23. DOI: 10.1158/0008-5472.CAN-12-0299. View

Waly Raphael S, Yangde Z, Yuxiang C . Hepatocellular carcinoma: focus on different aspects of management. ISRN Oncol. 2012; 2012:421673. PMC: 3359687. DOI: 10.5402/2012/421673. View

Murray G, Duncan M, Arbuckle E, Melvin W, Fothergill J . Matrix metalloproteinases and their inhibitors in gastric cancer. Gut. 1998; 43(6):791-7. PMC: 1727341. DOI: 10.1136/gut.43.6.791. View

Leong A . Diagnostic immunohistochemistry--problems and solutions. Pathology. 1992; 24(1):1-4. DOI: 10.3109/00313029209063611. View

Wright L, Yong S, Picken M, Rockey D, Fimmel C . Decreased survival and hepato-renal pathology in mice with C-terminally truncated GP73 (GOLPH2). Int J Clin Exp Pathol. 2008; 2(1):34-47. PMC: 2491393. View

Shiozaki H, Oka H, Inoue M, Tamura S, Monden M . E-cadherin mediated adhesion system in cancer cells. Cancer. 1996; 77(8 Suppl):1605-13. DOI: 10.1002/(SICI)1097-0142(19960415)77:8<1605::AID-CNCR28>3.0.CO;2-2. View

Kokkinos M, Wafai R, Wong M, Newgreen D, Thompson E, Waltham M . Vimentin and epithelial-mesenchymal transition in human breast cancer--observations in vitro and in vivo. Cells Tissues Organs. 2007; 185(1-3):191-203. DOI: 10.1159/000101320. View

Jemal A, Bray F, Center M, Ferlay J, Ward E, Forman D . Global cancer statistics. CA Cancer J Clin. 2011; 61(2):69-90. DOI: 10.3322/caac.20107. View

Shen R, Xie F, Shen H, Liu Q, Zheng T, Kou X . Negative correlation of LIV-1 and E-cadherin expression in hepatocellular carcinoma cells. PLoS One. 2013; 8(2):e56542. PMC: 3577881. DOI: 10.1371/journal.pone.0056542. View

10.

Radwan N, Ahmed N . The diagnostic value of arginase-1 immunostaining in differentiating hepatocellular carcinoma from metastatic carcinoma and cholangiocarcinoma as compared to HepPar-1. Diagn Pathol. 2012; 7:149. PMC: 3500209. DOI: 10.1186/1746-1596-7-149. View

11.

Yang Y, Xiao L, Mao R, Zhang H, Wen H, Zhao H . [Expression profiles and differential diagnostic value of serum Golgi protein-73 in patients with liver cirrhosis and primary hepatic carcinoma]. Zhonghua Gan Zang Bing Za Zhi. 2013; 20(12):920-4. DOI: 10.3760/cma.j.issn.1007-3418.2012.12.010. View

12.

Kladney R, Bulla G, Guo L, Mason A, Tollefson A, SIMON D . GP73, a novel Golgi-localized protein upregulated by viral infection. Gene. 2000; 249(1-2):53-65. PMC: 7127640. DOI: 10.1016/s0378-1119(00)00136-0. View

13.

Huang Q, Liu L, Liu C, Shao F, Xie F, Zhang C . Expression of Smad7 in cholangiocarcinoma: prognostic significance and implications for tumor metastasis. Asian Pac J Cancer Prev. 2012; 13(10):5161-5. DOI: 10.7314/apjcp.2012.13.10.5161. View

14.

Mima K, Hayashi H, Kuroki H, Nakagawa S, Okabe H, Chikamoto A . Epithelial-mesenchymal transition expression profiles as a prognostic factor for disease-free survival in hepatocellular carcinoma: Clinical significance of transforming growth factor-β signaling. Oncol Lett. 2012; 5(1):149-154. PMC: 3525349. DOI: 10.3892/ol.2012.954. View

15.

Mao Y, Yang H, Xu H, Lu X, Sang X, Du S . Golgi protein 73 (GOLPH2) is a valuable serum marker for hepatocellular carcinoma. Gut. 2010; 59(12):1687-93. DOI: 10.1136/gut.2010.214916. View

16.

Shi Y, Wu H, Zhang M, Ding L, Meng F, Fan X . Expression of the epithelial-mesenchymal transition-related proteins and their clinical significance in lung adenocarcinoma. Diagn Pathol. 2013; 8:89. PMC: 3671218. DOI: 10.1186/1746-1596-8-89. View

17.

Bukholm I, Nesland J, Karesen R, JACOBSEN U, Borresen-Dale A . E-cadherin and alpha-, beta-, and gamma-catenin protein expression in relation to metastasis in human breast carcinoma. J Pathol. 1998; 185(3):262-6. DOI: 10.1002/(SICI)1096-9896(199807)185:3<262::AID-PATH97>3.0.CO;2-Y. View

18.

Yang J, Mani S, Liu Donaher J, Ramaswamy S, Itzykson R, Come C . Twist, a master regulator of morphogenesis, plays an essential role in tumor metastasis. Cell. 2004; 117(7):927-39. DOI: 10.1016/j.cell.2004.06.006. View

19.

Parkin D . Global cancer statistics in the year 2000. Lancet Oncol. 2002; 2(9):533-43. DOI: 10.1016/S1470-2045(01)00486-7. View

20.

Sun Y, Yang H, Mao Y, Xu H, Zhang J, Li G . Increased Golgi protein 73 expression in hepatocellular carcinoma tissue correlates with tumor aggression but not survival. J Gastroenterol Hepatol. 2011; 26(7):1207-12. DOI: 10.1111/j.1440-1746.2011.06733.x. View