Vascular Endothelial Growth Factor Levels Difference among Hepatocellular Cancer Patients Based on Barcelona Clinic Liver Cancer Staging
DOI:
https://doi.org/10.3889/oamjms.2021.6598Keywords:
Barcelona clinic liver cancer, Carcinoma, Hepatocellular, Vascular endothelial growth factorAbstract
BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. It depends on angiogenesis for growth and metastasis. Vascular endothelial growth factor (VEGF), a growth factor for angiogenesis, is hoped to be a biomarker for the diagnosis of HCC and its development.
AIM: The objective of the study is to determine the difference of VEGF levels among HCC patients based on barcelona clinic liver cancer (BCLC) staging.
METHODS: A cross-sectional study was conducted at Haji Adam Malik General Hospital Medan, Indonesia between January and December 2018. Patients aged 18 years or older with HCC were enrolled using consecutive sampling method. Patients with cholangiocarcinoma, hemangioma, and liver metastasis were excluded from the study. The diagnosis of HCC was confirmed by triphasic computed tomography-scanning. Circulating VEGF levels were determined from serum specimen using Quantikine Human VEGF-enzyme-linked immunosorbent assay. All patients were grouped based on BCLC staging. Kruskal Wallis-H test was applied at 95% confidence interval. p < 0.05 was considered significant.
RESULTS: Of 60 patients, 47 (78.3%) were male. Mean age of patients was 61.4 (SD11.7) years. Hepatitis B was the most common etiology (70.0%) of HCC. Based on BCLC staging, 25 (41.7%) patients were in stage C. Median VEGF level was 951.25 pg/mL. There was a statistically significant difference in VEGF levels (p = 0.006) where patients in Stage C (1,009.6 pg/mL) and D (1,189.7 pg/mL) had higher VEGF levels compared to those in Stage A (578 pg/mL).
CONCLUSION: There was a statistically significant difference of VEGF levels among HCC patients based on BCLC staging.Downloads
Metrics
Plum Analytics Artifact Widget Block
References
Tang A, Chernyak V, Kamaya A, Sirlin CB. Epidemiology of hepatocellular carcinoma: target population for surveillance and diagnosis. Abdom Radiol. 2018;43(1):13-25. https://doi.org/10.1007/s00261-017-1209-1 PMid:28647765
Li Y, Zhai Z, Liu D, Zhong X, Meng X, Yang Q, et al. CD105 promotes hepatocarcinoma cell invasion and metastasis through VEGF. Tumour Biol. 2015;36(2):737-45. https://doi.org/10.1007/s13277-014-2686-2 PMid:25286761
Siregar GA. Nonsurgical treatment for hepatocellular carcinoma. Univ Med. 2011;21:35-42.
Butar-Butar AM. Profil Penderita Karsinoma Hepatoseluler di Rumah Sakit Umum Pusat Haji Adam Malik Medan pada tahun 2009-2012 [Thesis]. [Medan (North Sumatera)]: Universitas Sumatera Utara; 2013. https://doi.org/10.15851/jap.v4n2.819
He W, Xu M, Xu R, Zhou X, Ouyang J, Han H, et al. Inpatients’ knowledge about primary liver cancer and hepatitis. Asian Pac J Cancer Prev. 2013;14(8):4913-8. https://doi.org/10.7314/apjcp.2013.14.8.4913 PMid:24083767
Pazgan-Simon M, Serafinska S, Janocha-Litwin J, Simon K, Zuwala-Jagiello J. Diagnostic challenges in primary hepatocellular carcinoma: Case reports and review of the literature. Case Rep Oncol Med. 2015;2015:878763. https://doi.org/10.1155/2015/878763 PMid:25922775
Sharma BK, Srinivasan R, Kapil S, Singla B, Saini N, Chawla YK, et al. Serum levels of angiogenic and anti-angiogenic factors: their prognostic relevance in locally advanced hepatocellular carcinoma. Mol Cell Biochem. 2013;383(1-2):103-12. https://doi.org/10.1007/s11010-013-1759-7 PMid:23912396
Yang S, Yang C, Yu F, Ding W, Hu Y, Cheng F, et al. Endoplasmic reticulum resident oxidase ERO1-Lalpha promotes hepatocellular carcinoma metastasis and angiogenesis through the S1PR1/STAT3/VEGF-A pathway. Cell Death Dis. 2018;9:1105. https://doi.org/10.1038/s41419-018-1134-4
Saraswat VA, Pandey G, Shetty S. Treatment algorithms for managing hepatocellular carcinoma. J Clin Exp Hepatol. 2014;4(Suppl 3):S80-9. PMid:25755616
Chen H, Zhang Y, Li S, Li N, Chen Y, Zhang B, et al. Direct comparison of five serum biomarkers in early diagnosis of hepatocellular carcinoma. Cancer Manag Res. 2018;10:1947-58. https://doi.org/10.2147/cmar.s167036 PMid:30022853
Carr BI, Akkiz H, Üsküdar O, Yalçın K, Guerra V, Kuran S, et al. HCC with low- and normal-serum alpha-fetoprotein levels. Clin Pract (Lond). 2018;15(1):453-64. PMid:29576865
Mukozu T, Nagai H, Matsui D, Kanekawa T, Sumino Y. Serum VEGF as a tumor marker in patients with HCV-related liver cirrhosis and hepatocellular carcinoma. Anticancer Res. 2013;33(3):1013-21. https://doi.org/10.1016/s0016-5085(12)63799-8 PMid:23482775
Zhang L, Wang J, Tang J, Kong X, Yang J, Zheng F, et al. VEGF is essential for the growth and migration of human hepatocellular carcinoma cells. Mol Biol Rep. 2012;39(5):5085-93. PMid:22161247
Pang G, Duan Z, Shao C, Zhao F, Zhong H, Shao G. Heterogeneity analysis of triphasic CT scan perfusion parameters in differential diagnosis of hepatocellular carcinoma and hemangioma. Medicine (Baltimore). 2018;97(38):e12512. https://doi.org/10.1097/md.0000000000012512 PMid:30235766
Liu P, Xie SH, Hu S, Cheng X, Gao T, Zhang C, et al. Age-specific sex difference in the incidence of hepatocellular carcinoma in the United States. Oncotarget. 2017;8(40):68131-7. https://doi.org/10.18632/oncotarget.19245 PMid:28978103
Wu EM, Wong LL, Hernandez BY, Ji JF, Jia W, Kwee SA, et al. Gender differences in hepatocellular cancer: Disparities in nonalcoholic fatty liver disease/steatohepatitis and liver transplantation. Hepatoma Res. 2018;4:66. https://doi.org/10.20517/2394-5079.2018.87 PMid:30687780
Matsui D, Nagai H, Mukozu T, Ogino Y, Sumino Y. VEGF in patients with advanced hepatocellular carcinoma receiving intra-arterial chemotherapy. Anticancer Res. 2015;35(4):2205-10. PMid:25862879
Teixeira AC, Brasil IR, Torres AF, Tavora F. The evaluation of angiogenesis markers in hepatocellular carcinma and precursor lesions in liver explants from a single institution. Appl Immunohistochem Mol Morphol. 2018;26(5):330-6. https://doi.org/10.1097/pai.0000000000000426 PMid:27556821
Kinoshita A, Onoda H, Fushiya N, Koike K, Nishino H, Tajiri H. Staging systems for hepatocellular carcinoma: Current status and future perspectives. World J Hepatol. 2015;7(3):406-24. PMid:25848467
Darmadi D, Ruslie RH. Association between prothrombin induced by Vitamin K absence-II (PIVKA-II) and Barcelona clinic liver cancer (BCLC) stage, tumor size, portal venous thrombosis in hepatocellular carcinoma patients. Sains Malays. 2021;50:475-80. https://doi.org/10.17576/jsm-2021-5002-18
Watson CJ, Webb NJ, Bottomley MJ, Brenchley PE. Identification of polymorphisms within the vascular endothelial growth factor (VEGF) gene: Correlation with variation in VEGF protein production. Cytokine. 2000;12(8):1232-5. https://doi.org/10.1006/cyto.2000.0692 PMid:10930302
Wang W, Li G, Zhu J, Huang D, Zhou H, Zhong W, et al. Overexpression of AGGF1 is correlated with angiogenesis and poor prognosis of hepatocellular carcinoma. Med Oncol. 2015;32(4):131. https://doi.org/10.1007/s12032-015-0574-2 PMid:25796501
Campillo A, Solanas E, Morandeira MJ, Castiella T, Lorente S, Garcia-Gil FA, et al. Angiogenesis and proliferation markers in adjacent cirrhotic tissue could predict hepatocellular carcinoma outcome after liver transplantation. Eur J Gastroenterol Hepatol. 2014;26(8):871-9. https://doi.org/10.1097/meg.0000000000000131 PMid:24922356
Downloads
Published
How to Cite
Issue
Section
Categories
License
Copyright (c) 2020 Darmadi Darmadi, Riska Habriel Ruslie, Cennikon Pakpahan (Author)

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC 4.0)
