High expression of agrin is associated with tumor progression and poor prognosis in hepatocellular carcinoma

Qi-Jia Zhang; Li Wan; Han-Feng Xu

doi:10.3934/mbe.2019368

Mathematical Biosciences and Engineering, 2019, 16(6): 7375-7383. doi: 10.3934/mbe.2019368. Research article

Export file:

Format

RIS(for EndNote,Reference Manager,ProCite)
BibTex
Text

Content

Citation Only
Citation and Abstract

High expression of agrin is associated with tumor progression and poor prognosis in hepatocellular carcinoma

Qi-Jia Zhang, Li Wan, Han-Feng Xu

Department of Oncology,The Second Hospital of Nanjing, Nanjing University of Chinese Medicine,Nanjing, Jiangsu,210003,China

Received: , Accepted: , Published:

Abstract Full Text(HTML) Figure/Table Related pages

The heparan sulfate proteoglycan agrin is known to accumulate in the context of hepatocellular carcinoma (HCC). Agrin is important for neoangiogenesis in HCC tissues, and is incorporated into newly formed vasculature, but exactly how agrin contributes to the pathology of HCC remains to be fully defined. We therefore examined the clinical relevance of agrin as it pertains to HCC progression and prognosis using tissue sections from a total of 313 HCC patients. We found that agrin expression was detectable in more HCC samples (25.4% vs. 77.1%; P < 0.05) compared to normal tissue controls. Agrin expression was notably linked to tumor size (P = 0.041) and metastasis (P = 0.034). The recurrence free survival rate of agrin-positive HCC patients was considerably lower than that of agrin-negative patients (P = 0.001). We further confirmed HCC survival to be independently correlated with tumor size, metastasis, microvascular invasion and edmondson Grade via a Cox regression analysis. Upregulation of Agrin may play a crucial role in HCC progression. Together our results suggest that Agrin has the potential to be used as a prognostic indicator in predicting HCC patient outcomes.

Figure/Table

Supplementary

Article Metrics

Keywords: agrin; hepatocellular carcinoma; progression; prognosis

Citation: Qi-Jia Zhang, Li Wan, Han-Feng Xu. High expression of agrin is associated with tumor progression and poor prognosis in hepatocellular carcinoma. Mathematical Biosciences and Engineering, 2019, 16(6): 7375-7383. doi: 10.3934/mbe.2019368

References:

1. F. Bray, J. Ferlay, I. Soerjomataram, et al., Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries, CA-Cancer J. Clin., 68 (2018), 394–424.
2. S. F. Altekruse, K. A. McGlynn, L. A. Dickie, et al., Hepatocellular carcinoma confirmation, treatment, and survival in surveillance, epidemiology, and end results registries, 1992–2008, Hepatology, 55 (2012), 476–482.
3. S. Whittaker, R. Marais and A. X. Zhu, The role of signaling pathways in the development and treatment of hepatocellular carcinoma, Oncogene, 36 (2010), 4989–5005.
4. H. Huynh, R. W. Ong, P. Y. Li, et al ., Targeting receptor tyrosine kinase pathways in hepatocellular carcinoma, Anticancer Agents Med. Chem., 11 (2011), 560–575.
5. P. Kischel, F. Guillonneau, B. Dumont, et al ., Cell membrane proteomic analysis identifies proteins differentially expressed in osteotropic human breast cancer cells, Neoplasia, 10 (2018), 1014–1020.
6. P. Tátrai, A. Somorácz, E. Batmunkh, et al ., Agrin and CD34 immunohistochemistry for the discrimination of benign versus malignant hepatocellular lesions, Am. J. Surg. Pathol., 33 (2009), 874–885.
7. P. Tatrai, J. Dudas, E. Batmunkh, et al ., Agrin, a novel basement membrane component in human and rat liver, accumulates in cirrhosis and hepatocellular carcinoma, Lab Invest., 86 (2006), 1149–1160.
8. U. Winzen, G. J. Cole and W. Halfter, Agrin is a chimeric proteoglycan with the attachment sites for heparan sulfate/chondroitin sulfate located in two multiple serine-glycine clusters, J. Biol. Chem., 278 (2003), 30106–30114.
9. G. Bezakova and M. A. Ruegg, New insights into the roles of agrin, Nat. Rev. Mol. Cell Biol., 4 (2003), 295–308.
10. A. Somorácz, P. Tátrai, G. Horváth, et al., Agrin immunohistochemistry facilitates the determination of primary versus metastatic origin of liver carcinomas, Hum. Pathol., 41 (2010), 1310–1319.
11. M. Gautam, P. G. Noakes, L. Moscoso, et al., Defective neuromuscular synaptogenesis in agrin-deficient mutant mice, Cell, 85 (1996), 525.
12. E. Batmunkh, P. Tátrai, E. Szabó, et al., Comparison of the expression of agrin, a basement membrane heparan sulfate proteoglycan, in cholangiocarcinoma and hepatocellular carcinoma, Hum. Pathol., 38 (2007), 1508–1515.
13. L. C. van Kempen , D. J. Ruiter , G. N. van Muijen, et al., The tumor microenvironment: a critical determinant of neoplastic evolution, Eur. J. Cell Biol., 82 (2004), 539–548.
14. A. Naba, K. R. Clauser, S. Hoersch, et al., The Matrisome: In Silico Definition and In Vivo Characterization by Proteomics of Normal and Tumor Extracellular Matrices, Mol. Cell Proteom., 11 (2012): M111.014647.
15. U. Barash, V. Cohen-Kaplan, I. Dowek, et al., Proteoglycans in health and disease: new concepts for heparanase function in tumor progression and metastasis, FEBS J., 277 (2010), 3890–3903.
16. A. D. Theocharis, S. S. kandalis, G. N. Tzanakakis, et al., Proteoglycans in health and disease: novel roles for proteoglycans in malignancy and their pharmacological targeting, FEBS J., 277 (2010), 3904–3923.
17. R. V. Iozzo and R. D. Sanderson, Proteoglycans in cancer biology, tumour microenvironment and angiogenesis, J. Cell Mol. Med., 15 (2011), 1013–1031.
18. I. J. Edwards, Proteoglycans in prostate cancer, Nat. Rev. Urol., 9 (2012), 196–206.
19. C. Mundhenke, K. Meyer, S. Drew, et al., Heparan sulfate proteoglycans as regulators of fibroblast growth factor-2 receptor binding in breast carcinomas, Am. J. Pathol., 160 (2002): 185–194.

show all references

Reader Comments

your name: * your email: *

Download full text in PDF

Associated material

Metrics