Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
BMC Cancer
Published in: BMC Cancer 1/2023

Open Access 01-12-2023 | Hepatocellular Carcinoma | Research

Study of some potential biomarkers in Egyptian hepatitis C virus patients in relation to liver disease progression and HCC

Authors: Kholoud Baraka, Rania R. Abozahra, Eman Badr, Sarah M. Abdelhamid

Published in: BMC Cancer | Issue 1/2023

Login to get access

Abstract

Background

Egypt has the greatest prevalence of hepatitis C worldwide according to the WHO reports, accounting for 13% of the global HCV infections. HCV is a substantial precursor for fibrosis, cirrhosis, and hepatocellular carcinoma. This study aimed to investigate the potential relevance of some cytokines, miR-122 and miR-221 for the diagnosis of liver disease progression associated to HCV infection.

Methods

One hundred and twenty blood samples were collected from patients with chronic liver disease, HCC, and healthy individuals. Total bilirubin, alanine aminotransferase, aspartate aminotransferase, platelet count, albumin, and creatinine were measured. Serum level of selected cytokines was conducted by ELISA. Serum miRNA expression was detected by RT-PCR.

Results

IL-2R was higher among HCC patients and the mean concentration of both TNF-αRII and IL-6R was higher among cirrhotic patients. The expression of miRNA-122 showed a little fold decrease in all studied groups; the highest level was observed in HCC patients. The expression of miRNA-221 showed a significant fold increase in HCC and cirrhotic groups.

Conclusions

This study revealed that there is no difference in liver disease progression in patients regarding sex and age. Routine liver function tests performed poorly in terms of early diagnosis of liver disease progression; however, serum total bilirubin gave somewhat useful guide for discrimination between fibrotic, cirrhotic and HCC cases. IL-2R showed a significant consistent increase in its level with disease progression. The miR-221 serum level showed significant fold increase with liver disease progression. Therefore, making miR-221 a potential non-invasive biomarker for liver disease progression in the diagnostic setting is recommended.
Literature
1.
Roudot-Thoraval F. Epidemiology of hepatitis C virus infection. Clin Res Hepatol Gastroenterol. 2021;45(3):101596.PubMed
2.
Leumi S, El Kassas M, Zhong J. Hepatitis C virus genotype 4: a poorly characterized endemic genotype. J Med Virol. 2021;93(11):6079–88.PubMed
3.
El Kassas M, Elbaz T, Elsharkawy A, Omar H, Esmat G. HCV in Egypt, prevention, treatment and key barriers to elimination. Expert Rev anti-infective Therapy. 2018;16(4):345–50.PubMed
4.
Struthers A. From schistosomiasis to hepatitis C: the spread of HCV in Egypt. Med J Ther Afr. 2007;1(3).
5.
Hoofnagle JH. Hepatitis C: the clinical spectrum of disease. Hepatology. 1997;26(S3):15S–20S.PubMed
6.
Ruane PJ, Ain D, Stryker R, Meshrekey R, Soliman M, Wolfe PR, et al. Sofosbuvir plus ribavirin for the treatment of chronic genotype 4 hepatitis C virus infection in patients of Egyptian ancestry. J Hepatol. 2015;62(5):1040–6.PubMed
7.
Thomas DL. Global elimination of chronic hepatitis. N Engl J Med. 2019;380(21):2041–50.PubMed
8.
Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. Cancer J Clin. 2021;71(3):209–49.
9.
Llovet JM, Kelley RK, Villanueva A, Singal AG, Pikarsky E, Roayaie S, et al. Hepatocellular carcinoma. Nat Reviews Disease Primers. 2021;7(1):6.PubMed
10.
London WTPJ, McGlynn KA. Liver cancer. In: Thun MJ, Linet MS, Cerhan JR, Haiman CA, Schottenfeld DE. Cancer Epidemiology and Prevention. 2018:635–60.
11.
Ezzat R, Eltabbakh M, El Kassas M. Unique situation of hepatocellular carcinoma in Egypt: a review of epidemiology and control measures. World J Gastrointest Oncol. 2021;13(12):1919–38.PubMedPubMedCentral
12.
Lagos-Quintana M, Rauhut R, Yalcin A, Meyer J, Lendeckel W, Tuschl T. Identification of tissue-specific microRNAs from mouse. Curr Biol. 2002;12(9):735–9.PubMed
13.
Ludwig N, Leidinger P, Becker K, Backes C, Fehlmann T, Pallasch C, et al. Distribution of miRNA expression across human tissues. Nucleic Acids Res. 2016;44(8):3865–77.PubMedPubMedCentral
14.
Li W, Xie L, He X, Li J, Tu K, Wei L, et al. Diagnostic and prognostic implications of microRNAs in human hepatocellular carcinoma. Int J Cancer. 2008;123(7):1616–22.PubMed
15.
Jiang J, Gusev Y, Aderca I, Mettler TA, Nagorney DM, Brackett DJ, et al. Association of MicroRNA expression in hepatocellular carcinomas with hepatitis infection, cirrhosis, and patient survival. Clin Cancer Res. 2008;14(2):419–27.PubMedPubMedCentral
16.
Fornari F, Gramantieri L, Ferracin M, Veronese A, Sabbioni S, Calin G, et al. MiR-221 controls CDKN1C/p57 and CDKN1B/p27 expression in human hepatocellular carcinoma. Oncogene. 2008;27(43):5651–61.PubMed
17.
Budhu A, Wang XW. The role of cytokines in hepatocellular carcinoma. J Leukoc Biol. 2006;80(6):1197–213.PubMed
18.
De Lalla C, Galli G, Aldrighetti L, Romeo R, Mariani M, Monno A, et al. Production of profibrotic cytokines by invariant NKT cells characterizes cirrhosis progression in chronic viral hepatitis. J Immunol. 2004;173(2):1417–25.PubMed
19.
GamalEl Din SF, Motawi AT, Rashed LA, Elghobary H, Saad HM, Ismail MM, et al. Study of the role of microRNAs 16 and 135a in patients with lifelong premature ejaculation receiving fluoxetine daily for 3 months: a prospective case control study. Andrologia. 2022;54(10):e14549.PubMed
20.
Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2 – ∆∆CT method. Methods. 2001;25(4):402–8.PubMed
21.
22.
Kandeel A, Genedy M, El-Refai S, Funk AL, Fontanet A, Talaat M. The prevalence of hepatitis C virus infection in Egypt 2015: implications for future policy on prevention and treatment. Liver Int. 2017;37(1):45–53.PubMed
23.
Waked I, Doss W, El-Sayed MH, Estes C, Razavi H, Shiha G, et al. The current and future disease burden of chronic hepatitis C virus infection in Egypt. Arab J Gastroenterol. 2014;15(2):45–52.PubMed
24.
Elgharably A, Gomaa AI, Crossey MM, Norsworthy PJ, Waked I, Taylor-Robinson SD. Hepatitis C in Egypt–past, present, and future. Int J Gen Med. 2017;10:1.PubMed
25.
Conti F, Buonfiglioli F, Scuteri A, Crespi C, Bolondi L, Caraceni P, et al. Early occurrence and recurrence of hepatocellular carcinoma in HCV-related cirrhosis treated with direct-acting antivirals. J Hepatol. 2016;65(4):727–33.PubMed
26.
Reig M, Mariño Z, Perelló C, Iñarrairaegui M, Ribeiro A, Lens S, et al. Unexpected high rate of early tumor recurrence in patients with HCV-related HCC undergoing interferon-free therapy. J Hepatol. 2016;65(4):719–26.PubMed
27.
Yang JD, Aqel BA, Pungpapong S, Gores GJ, Roberts LR, Leise MD. Direct acting antiviral therapy and tumor recurrence after liver transplantation for hepatitis C-associated hepatocellular carcinoma. J Hepatol. 2016;65(4):859–60.PubMed
28.
Organization WH. Global health sector strategy on viral hepatitis 2016–2021. Towards ending viral hepatitis. World Health Organization; 2016.
29.
El-Serag HB. Hepatocellular carcinoma: an epidemiologic view. J Clin Gastroenterol. 2002;35(5):72–S8.
30.
Sun S, Poon RT, Lee NP, Yeung C, Chan K, Ng IO, et al. Proteomics of hepatocellular carcinoma: serum vimentin as a surrogate marker for small tumors (≤ 2 cm). J Proteome Res. 2010;9(4):1923–30.PubMed
31.
Zhong M, Zhai X, Lin W, Liu Q, Yao M, Guo Y, et al. Serum interleukin-8 as an indicator of tumor recurrence in hepatocellular carcinoma after transarterial chemoembolization. Volume 13. INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL MEDICINE; 2020. pp. 3540–7. 5.
32.
Iwane K, Kayahara T, Takahata H, Morimoto Y, Iseki A, Mizuno M, et al. A case of malignant lymphoma recurrence immediately after the end of direct-acting antivirals for hepatitis C. J Japanese Soc Gastroenterol. 2019;116(2):177–83.
33.
He C, Wei Q, Zhu J, Qin Q, Wang H, Liu S. Clinical value of assessing serum levels of inflammatory cytokines in the early diagnosis of patients with primary liver carcinoma: a retrospective observational study. J Bio-X Res. 2021;04(01):29–35.
34.
Izzo F, Curley S, Maio P, Leonardi E, Imparato L, Giglio S, et al. Correlation of soluble interleukin-2 receptor levels with severity of chronic hepatitis C virus liver injury and development of hepatocellular cancer. Surgery. 1996;120(1):100–5.PubMed
35.
36.
Damoiseaux J. The IL-2 – IL-2 receptor pathway in health and disease: the role of the soluble IL-2 receptor. Clin Immunol. 2020;218:108515.PubMed
37.
Zhang M, Zhang S, Yang Z, Hu J, Hu W, Sun P, et al. Association between the expression levels of IL–6 and IL–6R in the hepatocellular carcinoma microenvironment and postoperative recurrence. Oncol Lett. 2018;16(6):7158–65.PubMedPubMedCentral
38.
Tanaka T, Narazaki M, Kishimoto T. IL-6 in inflammation, immunity, and disease. Cold Spring Harb Perspect Biol. 2014;6(10):a016295.PubMedPubMedCentral
39.
Srivastava A, Sharma H, Khanna S, Sadhu Balasundaram T, Chowdhury S, Chowdhury R, et al. Interleukin-6 Induced Proliferation is attenuated by transforming growth Factor-β-Induced Signaling in Human Hepatocellular Carcinoma cells. Front Oncol. 2022;11:811941.PubMedPubMedCentral
40.
Zekri A-RN, Ashour MSE-D, Hassan A, Alam El-Din HM, El-Shehaby AMR, Abu-Shady MA. Cytokine profile in Egyptian hepatitis C virus genotype-4 in relation to liver disease progression. World J Gastroenterol. 2005;11(42):6624–30.PubMedPubMedCentral
41.
Kakumu S, Okumura A, Ishikawa T, Yano M, Enomoto A, Nishimura H, et al. Serum levels of IL-10, IL-15 and soluble tumour necrosis factor-alpha (TNF-α) receptors in type C chronic liver disease. Clin Experimental Immunol. 1997;109(3):458–63.
42.
Chia CS, Ban K, Ithnin H, Singh H, Krishnan R, Mokhtar S, et al. Expression of interleukin-18, interferon-γ and interleukin-10 in hepatocellular carcinoma. Immunol Lett. 2002;84(3):163–72.PubMed
43.
Ratti M, Lampis A, Ghidini M, Salati M, Mirchev MB, Valeri N, et al. MicroRNAs (miRNAs) and long non-coding RNAs (lncRNAs) as New Tools for Cancer Therapy: first steps from Bench to Bedside. Target Oncol. 2020;15(3):261–78.PubMedPubMedCentral
44.
Sohel MMH. Circulating microRNAs as biomarkers in cancer diagnosis. Life Sci. 2020;248:117473.PubMed
45.
Shimakami T, Yamane D, Jangra RK, Kempf BJ, Spaniel C, Barton DJ et al. Stabilization of hepatitis C virus RNA by an Ago2–miR-122 complex. Proceedings of the National Academy of Sciences. 2012;109(3):941-6.
46.
Shafiq A, Afzal N, Kashif M. Hepatitis C and hepatocellular carcinoma: a review of natural history. J Med Radiol Pathol Surg. 2016;2(3):23–9.
47.
Zhou J, Yu L, Gao X, Hu J, Wang J, Dai Z, et al. Plasma MicroRNA panel to diagnose Hepatitis B virus–related Hepatocellular Carcinoma. J Clin Oncol. 2011;29(36):4781–8.PubMed
48.
Tan Y, Ge G, Pan T, Wen D, Chen L, Yu X, et al. A serum microRNA panel as potential biomarkers for hepatocellular carcinoma related with hepatitis B virus. PLoS ONE. 2014;9(9):e107986.PubMedPubMedCentral
49.
Xu J, Wu C, Che X, Wang L, Yu D, Zhang T, et al. Circulating microRNAs, miR-21, miR‐122, and miR‐223, in patients with hepatocellular carcinoma or chronic hepatitis. Mol Carcinog. 2011;50(2):136–42.PubMed
50.
Qi P, Cheng S-q, Wang H, Li N, Chen Y-f. Gao C-f. serum microRNAs as biomarkers for hepatocellular carcinoma in Chinese patients with chronic hepatitis B virus infection. PLoS ONE. 2011;6(12):e28486.PubMedPubMedCentral
51.
Jin Y, Wong YS, Goh BKP, Chan CY, Cheow PC, Chow PKH, et al. Circulating microRNAs as potential diagnostic and prognostic biomarkers in Hepatocellular Carcinoma. Sci Rep. 2019;9(1):10464.PubMedPubMedCentral
52.
Liu Z, Wang C, Jiao X, Zhao S, Liu X, Wang Y, et al. miR-221 promotes growth and invasion of hepatocellular carcinoma cells by constitutive activation of NFκB. Am J Translational Res. 2016;8(11):4764.
53.
Ding C-L, Xu G, Ren H, Zhao L-J, Zhao P, Qi Z-T, et al. HCV infection induces the upregulation of miR-221 in NF-κB dependent manner. Virus Res. 2015;196:135–9.PubMed
54.
Xu G, Yang F, Ding C-L, Wang J, Zhao P, Wang W, et al. MiR-221 accentuates IFN׳ s anti-HCV effect by downregulating SOCS1 and SOCS3. Virology. 2014;462:343–50.PubMed
55.
Sohn W, Kim J, Kang SH, Yang SR, Cho J-Y, Cho HC, et al. Serum exosomal microRNAs as novel biomarkers for hepatocellular carcinoma. Exp Mol Med. 2015;47(9):e184–e.PubMedPubMedCentral
56.
Li J, Wang Y, Yu W, Chen J, Luo J. Expression of serum miR-221 in human hepatocellular carcinoma and its prognostic significance. Biochem Biophys Res Commun. 2011;406(1):70–3.PubMed
57.
Nagy Á, Lánczky A, Menyhárt O, Győrffy B. Validation of miRNA prognostic power in hepatocellular carcinoma using expression data of independent datasets. Sci Rep. 2018;8(1):9227.PubMedPubMedCentral
Metadata
Title
Study of some potential biomarkers in Egyptian hepatitis C virus patients in relation to liver disease progression and HCC
Authors
Kholoud Baraka
Rania R. Abozahra
Eman Badr
Sarah M. Abdelhamid
Publication date
01-12-2023
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2023
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-023-11420-1

Other articles of this Issue 1/2023

BMC Cancer 1/2023 Go to the issue

Research article

High-dose chemotherapy with stem cell rescue to treat stage III homologous deficient breast cancer: factors influencing clinical implementation

Research

Estrogen-related genes for thyroid cancer prognosis, immune infiltration, staging, and drug sensitivity

Research

Association of high-risk comorbidity with overall survival among patients with gastric cancer and its sex-specific differences in China: a retrospective observational cohort study

Study Protocol

Promoting physical activity through supervised vs motivational behavior change interventions in breast cancer survivors on aromatase inhibitors (PAC-WOMAN): protocol for a 3-arm pragmatic randomized controlled trial

Research

High USP32 expression contributes to cancer progression and is correlated with immune infiltrates in hepatocellular carcinoma

Research

Identification of novel tumor-associated antigens and evaluation of a panel of autoantibodies in detecting oral cancer
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits