Generic placeholder image

Current Pharmaceutical Analysis


ISSN (Print): 1573-4129
ISSN (Online): 1875-676X

Research Article

Identification of Candidate Biomarkers for HCV Leading to Hepatocellular Carcinoma Differential Stages From Serum Samples

Author(s): Amber Afroz*, Saba Saleem, Kalsoom Sughra, Sabaz Ali Khan and Nadia Zeeshan*

Volume 16, Issue 3, 2020

Page: [262 - 272] Pages: 11

DOI: 10.2174/1573412914666180912111038

Price: $65


Background: Hepatocellular carcinoma (HCC) is one of the most deadly liver malignancy found and Hepatitis C virus (HCV) is a prominent risk factor for this disease. Prognosis of HCC is poor; initiate the need of markers to discover therapeutic targets in HCC.

Introduction: Clinical staging systems of HCC composed of tumor characteristics along with liver function test are important in prognosis but they are not precise. Molecular profiling can lead to a better understanding of the physiopathology of HCC and can help in the development of novel therapeutic approaches.

Methods: 64 HCC serum samples (shifted from HCV) were graded into stage I- IV; along with +ive (3 Hepatitis C) and -ive control (2 healthy persons). Proteins were separated by sodium dodecyl sulfatepolyacrylamide gel electrophoresis (SDS-PAGE) and differential mRNA expression from serum samples of different HCC stages was confirmed by Real Time Polymerase Chain Reaction (qPCR).

Results: HCC serum proteins displayed differential expression of glutathione s-transferase (GST), glypican-3 (GPC3), vitronectin (VTN), and clusterin (CLU) by SDS-PAGE. GST was expressed in -ive control, while GPC3 was found in both -ive and +ive control. The qPCR analysis, display more than 0.07 fold decrease in GST in I-IV HCC stages. The highest increase in HCC stages was observed by GPC3; about 4 fold increase in I-IV stages. VTN show 1.7-3.4 fold; while CLU show 2-3.5 fold increase in four stages of HCC.

Conclusion: GPC3, VTN and CLU in combination can be good potential markers for differentiating stages (I-IV) of HCC.

Keywords: Hepatocellular carcinoma, vitronectin, glypican 3, clusterin, SDS-PAGE, glutathione S transferase.

Graphical Abstract
Pan, H.; Fu, X.; Huang, W. Molecular mechanism of liver cancer. Anticancer. Agents Med. Chem., 2011, 11(6), 493-499.
[] [PMID: 21554201]
Alavian, S.M.; Haghbin, H. Relative Importance of Hepatitis B and C Viruses in hepatocellular carcinoma in EMRO countries and the middle East: a systematic review. Hepat. Mon., 2016, 16(3)e35106
[] [PMID: 27226803]
Boutari, C.; Lefkos, P.; Athyros, V.G.; Karagiannis, A.; Tziomalos, K. Nonalcoholic fatty liver disease vs. nonalcoholic steatohepatitis: Pathological and clinical implications. Curr. Vasc. Pharmacol., 2018, 16(3), 214-218.
[] [PMID: 28676025]
Azer, S.A. MDM2-p53 Interactions in human hepatocellular carcinoma: What is the role of nutlins and new therapeutic options? J. Clin. Med., 2018, 7(4), 64.
[] [PMID: 29584707]
Wan, J-Y.; Sun, Z-L.; Zhang, Y-Z.; Wei, C-B.; Wang, C-Z.; Zhou, L-D. Searching for potential biomarkers of Penthorum chinese Pursh by extraction method and HPLC-MS analysis integrated with evaluation of hepatoprotective effect. Curr. Pharm. Anal., 2018, 14(4), 389-396.
Rojas, A.; Sanchez-Torrijos, Y.; Gil-Gomez, A.; Liu, C-H.; Rodriguez-Rivas, C.; Ferrer, M.T. Performance of different biomarkers for the management of hepatocellular carcinoma. Hepatoma Res., 2018, 4, 31.
Lou, J.; Zhang, L.; Lv, S.; Zhang, C.; Jiang, S. Biomarkers for hepatocellular carcinoma. Biomark. Cancer, 2017, 9, 1-9.
[] [PMID: 28469485]
Henderson, J.M.; Polak, N.; Chen, J.; Roediger, B.; Weninger, W.; Kench, J.G.; McCaughan, G.W.; Zhang, H.E.; Gorrell, M.D. Multiple liver insults synergize to accelerate experimental hepatocellular carcinoma. Sci. Rep., 2018, 8(1), 10283.
[] [PMID: 29980757]
Liu, H.; Yang, C.; Lu, W.; Zeng, Y. Prognostic significance of glypican-3 expression in hepatocellular carcinoma: A meta-analysis. Medicine (Baltimore), 2018, 97(4)e9702
[] [PMID: 29369198]
Xue, R.; Feng, J.; Meng, Q.; Lv, F.; Zhu, Y.; Yu, H.; Zhang, S.; Song, C.; Sun, L.; Yue, Z.; Feng, S.; Che, R.; Xiang, Q.; Jing, X. The significance of glypican-3 expression profiling in the tumor cellular origin theoretical system for hepatocellular carcinoma progression. J. Gastroenterol. Hepatol., 2017, 32(8), 1503-1511.
[] [PMID: 28087980]
Yang, X.P.; Zhou, L.X.; Yang, Q.J.; Liu, L.; Cai, Y.; Ma, S.L. Diagnostic and prognostic roles of serum vitronectin in hepatitis B-related hepatocellular carcinoma. Cancer Biomark., 2016, 17(3), 271-279.
[] [PMID: 27802203]
Zhong, J.; Yu, X.; Dong, X.; Lu, H.; Zhou, W.; Li, L. Downregulation of secreted clusterin potentiates the lethality of sorafenib in hepatocellular carcinoma in association with the inhibition of ERK1/2 signals. Int. J. Mol. Med., 2018, 41(5), 2893-2900.
Chauhan, R.; Lahiri, N. Tissue- and Serum-associated biomarkers of hepatocellular carcinoma. Biomark. Cancer, 2016, 8(S1)(Suppl. 1), 37-55.
[] [PMID: 27398029]
Fattahi, S.; Kazemipour, N.; Valizadeh, J.; Hashemi, M.; Ghazizade, H. Comparison of different albumin removal methods for evaluation of human serum proteome. Zahedan J. Res. Med. Sci., 2012, 14(4), 1-5.
Colantonio, D.A.; Dunkinson, C.; Bovenkamp, D.E.; Van Eyk, J.E. Effective removal of albumin from serum. Proteomics, 2005, 5(15), 3831-3835.
[] [PMID: 16145708]
Jain, R.K.; Jawade, A.A.; Pingle, S.K.; Tumane, R.G.; Thakkar, L.R. Separation of low molecular weight serum proteins using acetonitrile precipitation assessed by one dimensional gel electrophoresis. Eur. J. Exp. Biol., 2015, 5(5), 18-23.
Bradford, M.M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal. Biochem., 1976, 72, 248-254.
[] [PMID: 942051]
Simms, D.; Cizdziel, P.E.; Chomczynski, P. TRIzol: A new reagent for optimal single-step isolation of RNA. Focus, 1993, 15(4), 532-535.
Chandramouli, K.; Qian, P-Y. Proteomics: challenges, techniques and possibilities to overcome biological sample complexity. Hum. Genomics and Proteomics, 2009, 22. Article ID 239204
Li, T.; Zhao, X-P.; Wang, L-Y.; Gao, S.; Zhao, J.; Fan, Y-C.; Wang, K. Glutathione S-transferase P1 correlated with oxidative stress in hepatocellular carcinoma. Int. J. Med. Sci., 2013, 10(6), 683-690.
[] [PMID: 23569432]
Allocati, N.; Masulli, M.; Di Ilio, C.; Federici, L. Glutathione transferases: substrates, inihibitors and pro-drugs in cancer and neurodegenerative diseases. Oncogenesis, 2018, 7(1), 8.
[] [PMID: 29362397]
Trevisani, F. What is the role of biomarkers in diagnosis, prognosis and surveillance? EASL Home of Hepatology HCC summit; Geneva Swizerland, 2018, pp. 1-3.
Hwang, H.; Lee, J.Y.; Lee, H.K.; Park, G.W.; Jeong, H.K.; Moon, M.H.; Kim, J.Y.; Yoo, J.S. In-depth analysis of site-specific N-glycosylation in vitronectin from human plasma by tandem mass spectrometry with immunoprecipitation. Anal. Bioanal. Chem., 2014, 406(30), 7999-8011.
[] [PMID: 25374123]
Yao, M.; Fang, M.; Zheng, W.; Dong, Z.; Yao, D. Role of secretory clusterin in hepatocarcinogenesis. Transl. Gastroenterol. Hepatol., 2018, 3, 48.
[] [PMID: 30221206]
Jiang, H-Y.; Chen, J.; Xia, C-C.; Cao, L-K.; Duan, T.; Song, B. Noninvasive imaging of hepatocellular carcinoma: From diagnosis to prognosis. World J. Gastroenterol., 2018, 24(22), 2348-2362.
[] [PMID: 29904242]
Roberts, L.R.; Sirlin, C.B.; Zaiem, F.; Almasri, J.; Prokop, L.J.; Heimbach, J.K.; Murad, M.H.; Mohammed, K. Imaging for the diagnosis of hepatocellular carcinoma: A systematic review and meta-analysis. Hepatology, 2018, 67(1), 401-421.
[] [PMID: 28859233]
Russo, F.P.; Imondi, A.; Lynch, E.N.; Farinati, F. When and how should we perform a biopsy for HCC in patients with liver cirrhosis in 2018? A review. Dig. Liver Dis., 2018, 50(7), 640-646.
[] [PMID: 29636240]
Kimura, A.; Sogawa, K.; Satoh, M.; Kodera, Y.; Yokosuka, O.; Tomonaga, T.; Nomura, F. The application of a three-step serum proteome analysis for the discovery and identification of novel biomarkers of hepatocellular carcinoma. Int. J. Proteomics, 2012, 2012623190
[] [PMID: 22957256]
Zhu, W.; Li, W.; Yang, G.; Fu, C.; Jiang, G.; Hu, Q. Vitronectin silencing inhibits hepatocellular carcinoma in vitro and in vivo. Future Oncol., 2015, 11(2), 251-258.
[] [PMID: 25179307]
Zheng, W.; Yao, M.; Sai, W.; Qian, Q.; Pan, L.; Qiu, L.; Huang, J.; Wu, W.; Yao, D. Diagnostic and prognostic significance of secretory clusterin expression in patients with hepatocellular carcinoma. Tumour Biol., 2016, 37(1), 999-1008.
[] [PMID: 26264614]
Wang, C.; Jiang, K.; Gao, D.; Kang, X.; Sun, C.; Zhang, Q.; Li, Y.; Sun, L.; Zhang, S.; Guo, K.; Liu, Y. Clusterin protects hepatocellular carcinoma cells from endoplasmic reticulum stress induced apoptosis through GRP78. PLoS One, 2013, 8(2)e55981
[] [PMID: 23457489]

Rights & Permissions Print Export Cite as
© 2022 Bentham Science Publishers | Privacy Policy