TGF-1 mRNA, AFP-L3, and Annexin II in the Early and Late Detection of Hepatocellular Carcinoma: The Diagnostic Value

Eman  Youssef; Nashwa El-Khouly; Yahia Abdullah Elzahrani; Rehab M. E.  Tash; Eman A. Khalifa; Eman S. M. Bayoumy; Mona  Khalil; Awatif E. Edreis; Fatma Saffeyeldin Mohamed; Aml E. Abdou; Nora Seliem; Mahmoud Sofy; Sara Fakhrelden; Sohaila M. H. Marmoush; Ghada F.  Elmohaseb; Amal A.  Elhosary

doi:10.3889/oamjms.2022.10814

Authors

Eman Youssef Department of Biochemistry, Faculty of Medicine, Al-Azhar University, Nasr, Cairo, Egypt; Department of Biochemistry, College of Medicine, Taif University, Taif, Saudi Arabia
Nashwa El-Khouly Department of Internal Medicine, Faculty of Medicine, Al-Azhar University, Nasr, Cairo, Egypt
Yahia Abdullah Elzahrani Department of Internal Medicine, College of Medicine, Taif University, Taif, Saudi Arabia
Rehab M. E. Tash Department of Medical Microbiology and Immunology, Faculty of Medicine, Zagazig University, Zagazig, Egypt
Eman A. Khalifa Department of Parasitology, Faculty of Medicine, Tanta University, Tanta, Egypt; Department of Parasitology, College of Medicine, Taif University, Taif, Saudi Arabia
Eman S. M. Bayoumy Department of Biochemistry, Faculty of Medicine, Al-Azhar University, Nasr, Cairo, Egypt; Department of Biochemistry, College of Medicine, Taif University, Taif, Saudi Arabia
Mona Khalil Department of Biochemistry, Faculty of Medicine, Al-Azhar University, Nasr, Cairo, Egypt https://orcid.org/0000-0002-4529-6381
Awatif E. Edreis Department of Tropical Medicine, Faculty of Medicine, Tanta University, Tanta, Egypt; Department of Internal Medicine, College of Medicine, Taif University, Taif, Saudi Arabia
Fatma Saffeyeldin Mohamed Department of Internal Medicine, College of Medicine, Taif University, Taif, Saudi Arabia; Department of Tropical Medicine, Faculty of Medicine, Al-Azhar University, Nasr, Cairo, Egypt
Aml E. Abdou Department of Microbiology and Immunology, Faculty of Medicine, Al-Azhar University, Nasr, Cairo, Egypt
Nora Seliem Department of Biochemistry, Faculty of Medicine, Al-Azhar University, Nasr, Cairo, Egypt https://orcid.org/0000-0001-9541-6479
Mahmoud Sofy Department of Botany and Microbiology, Faculty of Science, Al-Azhar University, Nasr, Cairo, Egypt
Sara Fakhrelden Department of Tropical, Faculty of Medicine, Fayoum University, Fayoum, Egypt
Sohaila M. H. Marmoush Deparmtent of Biomedical Science, Faculty of Medical Sciences, Newcastle University Medicine Malaysia, Johor, Malaysia
Ghada F. Elmohaseb Department of Internal Medicine, Faculty of Medicine, Al-Azhar University, Nasr, Cairo, Egypt
Amal A. Elhosary Deparmtent of Clinical Pathology, Faculty of Medicine, Menoufia University, Shebin ElKoum, Egypt

DOI:

https://doi.org/10.3889/oamjms.2022.10814

Keywords:

HCC, tumor markers, AFP-L3, Annexin II, TGF-β1 gene expression

Abstract

BACKGROUND: Alpha-fetoprotein (AFP) is the recommended screening biomarker for hepatocellular carcinoma (HCC), despite its drawbacks: AFP-negative HCC, poor specificity, and sensitivity. As a result, new HCC-sensitive and specific biomarkers are urgently needed.

AIM: This study aimed to determine the diagnostic value of transforming growth factor (TGF)-β1 mRNA and Annexin II in the early detection and follow-up of HCC.

PATIENT AND METHODS: This research involved 75 HCC patients (30 early and 45 late) and 75 liver cirrhosis (LC) patients (all patients have HCV), and 75 healthy individuals as controls. Reverse transcription polymerase chain reaction measured TGF-β1 mRNA. Enzyme-linked immunosorbent assay ELISA measured Annexin II, AFP-L3, and AFP.

RESULTS: Annexin II was a biomarker with a significant difference between the LC and early HCC groups. TGF-β1 mRNA showed a significant difference when the LC group was compared to the control group and the late HCC group.

CONCLUSION: Annexin II has better sensitivity and specificity for early HCC detection than AFP, and TGF-β1 mRNA can be used for the assessment of the degree of HCC, and TGF-1 signaling inhibitors may be a possible new treatment choice for HCC.

Downloads

Download data is not yet available.

Metrics

Metrics Loading ...

Plum Analytics Artifact Widget Block

References

Kim S, Seo YS, Lee HA, Kim MN, Lee EJ, Shin HJ, et al. Hepatocellular carcinoma risk steadily persists over time despite long-term antiviral therapy for hepatitis B: A multicenter study. Cancer Epidemiol Biomarkers Prev. 2020;29(4):832-7. https://doi.org/10.1158/1055-9965.EPI-19-061 PMid:31988073 DOI: https://doi.org/10.1158/1055-9965.EPI-19-0614

El-Sheshtawy HS, Sofy MR, Ghareeb DA, Yacout GA, Eldemellawy MA, Ibrahim BM. Eco-friendly polyurethane acrylate (PUA)/natural filler-based composite as an antifouling product for marine coating. Appl Microbiol Biotechnol. 2021;105(18):7023-34. https://doi.org/10.1007/s00253-021-11501-w PMid:34477938 DOI: https://doi.org/10.1007/s00253-021-11501-w

Simmons O, Fetzer DT, Yokoo T, Marrero JA, Yopp A, Kono Y, et al. Predictors of adequate ultrasound quality for hepatocellular carcinoma surveillance in patients with cirrhosis. Aliment Pharmacol Ther. 2017;45(1):169-77. https://doi.org/10.1111/apt.13841 PMid:27862091 DOI: https://doi.org/10.1111/apt.13841

Tzartzeva K, Obi J, Rich NE, Parikh ND, Marrero JA, Yopp A, et al. Surveillance imaging and alpha fetoprotein for early detection of hepatocellular carcinoma in patients with cirrhosis: A meta-analysis. Gastroenterology. 2018;154(6):1706-8.e1. https://doi.org/10.1053/j.gastro.2018.01.064 PMid:29425931 DOI: https://doi.org/10.1053/j.gastro.2018.01.064

Stefaniuk P, Cianciara J, Wiercinska-Drapalo A. Present and future possibilities for early diagnosis of hepatocellular carcinoma. World J Gastroenterol. 2010;16(4):418-24. https://doi.org/10.3748/wjg.v16.i4.418 PMid:20101765 DOI: https://doi.org/10.3748/wjg.v16.i4.418

Zhu K, Dai Z, Zhou J. Biomarkers for hepatocellular carcinoma: Progression in early diagnosis, prognosis, and personalized therapy. Biomark Res. 2013;1(1):10. https://doi.org/10.1186/2050-7771-1-10 PMid:24252133 DOI: https://doi.org/10.1186/2050-7771-1-10

Omar A, Abou-Alfa GK, Khairy A, Omar H. Risk factors for developing hepatocellular carcinoma in Egypt. Chin Clin Oncol. 2013;2(4):43. https://doi.org/10.3978/j.issn.2304-3865.2013.11.07 PMid:25841922

Marrero JA, Lok AS. Newer markers for hepatocellular carcinoma. Gastroenterology. 2004;127(5 Suppl 1):S113-9. https://doi.org/10.1053/j.gastro.2004.09.024 PMid:15508074 DOI: https://doi.org/10.1053/j.gastro.2004.09.024

Li D, Mallory T, Satomura S. AFP-L3: A new generation of tumor marker for hepatocellular carcinoma. Clin Chim Acta. 2001;313(1- 2):15-9. https://doi.org/10.1016/s0009-8981(01)00644-1 PMid:11694234 DOI: https://doi.org/10.1016/S0009-8981(01)00644-1

Gerke V, Moss SE. Annexins: From structure to function. Physiol Rev. 2002;82(2):331-71. https://doi.org/10.1152/physrev.00030.2001 PMid:11917092 DOI: https://doi.org/10.1152/physrev.00030.2001

Kittaka N, Takemasa I, Takeda Y, Marubashi S, Nagano H, Umeshita K, et al. Molecular mapping of human hepatocellular carcinoma provides deeper biological insight from genomic data. Eur J Cancer. 2008;44(6):885-97. https://doi.org/10.1016/j.ejca.2008.02.019 PMid:18337085 DOI: https://doi.org/10.1016/j.ejca.2008.02.019

Yamazaki K, Masugi Y, Sakamoto M. Molecular pathogenesis of hepatocellular carcinoma: Altering transforming growth factor-β signaling in hepatocarcinogenesis. Dig Dis. 2011;29(3):284-8. https://doi.org/10.1159/000327560 PMid:21829019 DOI: https://doi.org/10.1159/000327560

Llovet JM, Fuster J, Bruix J, Barcelona-Clínic Liver Cancer Group. The Barcelona approach: Diagnosis, staging, and treatment of hepatocellular carcinoma. Liver Transpl. 2004;10(2 Suppl 1):S115-20. https://doi.org/10.1002/lt.20034 PMid:14762851 DOI: https://doi.org/10.1002/lt.20034

El-Sheshtawy HS, Mahdy HM, Sofy AR, Sofy MR. Production of biosurfactant by Bacillus megaterium and its correlation with lipid peroxidation of Lactuca sativa. Egypt J Pet. 2022;31(2):1-6. https://doi.org/10.1016/j.ejpe.2022.03.001 DOI: https://doi.org/10.1016/j.ejpe.2022.03.001

Agha MS, Abbas MA, Sofy MR, Haroun SA, Mowafy AM. Dual inoculation of Bradyrhizobium and Enterobacter alleviates the adverse effect of salinity on glycine max seedling. Not Bot Horti Agrobot Cluj Napoca. 2021;49(3):12461. https://doi.org/10.15835/nbha49312461 DOI: https://doi.org/10.15835/nbha49312461

Kumar V, Abbas AK, Aster JC. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Philadelphia, PA: Elsevier Saunders; 2015.

Zhang HJ, Yao DF, Yao M, Huang H, Wu W, Yan MJ, et al. Expression characteristics and diagnostic value of annexin A2 in hepatocellular carcinoma. World J Gastroenterol. 2012;18(41):5897-904. https://doi.org/10.3748/wjg.v18. i41.5897 PMid:23139605 DOI: https://doi.org/10.3748/wjg.v18.i41.5897

Shaker MK, Fattah HI, Sabbour GS, Montasser IF, Abdelhakam SM, El Hadidy E, et al. Annexin A2 as a biomarker for hepatocellular carcinoma in Egyptian patients. World J Hepatol. 2017;9(9):469-76. https://doi.org/10.4254/wjh.v9.i9.469 PMid:28396717 DOI: https://doi.org/10.4254/wjh.v9.i9.469

El-Abd N, Fawzy A, Elbaz T, Hamdy S. Evaluation of annexin A2 and as potential biomarkers for hepatocellular carcinoma. Tumor Biol. 2016;37(1):211-6. https://doi.org/10.1007/s13277-015-3524-x PMid:26189841 DOI: https://doi.org/10.1007/s13277-015-3524-x

Zhang J, Chen G, Zhang P, Zhang J, Li X, Gan D, et al. The threshold of alpha-fetoprotein (AFP) for the diagnosis of hepatocellular carcinoma: A systematic review and meta analysis. PLoS One. 2020;15(2):e0228857. https://doi.org/10.1371/journal.pone.0228857 PMid:32053643 DOI: https://doi.org/10.1371/journal.pone.0228857

Chen CY, Lin YS, Chen CH, Chen YJ. Annexin A2-mediated cancer progression and therapeutic resistance in nasopharyngeal carcinoma. J Biomed Sci. 2018;25(1):30. https://doi.org/10.1186/s12929-018-0430-8 PMid:29598816 DOI: https://doi.org/10.1186/s12929-018-0430-8

Zhuang C, Wang P, Sun T, Zheng L, Ming L. Expression levels and prognostic values of annexins in liver cancer. Oncol Lett. 2019;18(6):6657-9. https://doi.org/10.3892/ol.2019.11025 PMid:31807177 DOI: https://doi.org/10.3892/ol.2019.11025

Chen S, Li J, Tan X, Xu Q, Mo Y, Qin H, et al. Clinical role of combining alpha-fetoprotein and lens culinaris agglutinin reactive fraction of alpha-fetoprotein for hepatocellular carcinoma: Evidence from literature and an original study. J Clin Lab Anal. 2020;34(7):e23262. https://doi.org/10.1002/jcla.23262 PMid:32167614 DOI: https://doi.org/10.1002/jcla.23262

Durazo F, Blatt L, Corey WG, Lin JH, Han S, Saab S, et al. Des γ-carboxyprothrombin, α-fetoprotein and AFP-L3 in patients with chronic hepatitis, cirrhosis and hepatocellular carcinoma. J Gastroenterol Hepatol. 2008;23(10):1541-8. https://doi.org/10.1111/j.1440-1746.2008.05395.x PMid:18422961 DOI: https://doi.org/10.1111/j.1440-1746.2008.05395.x

Principe DR, Doll JA, Bauer J, Jung B, Munshi HG, Bartholin L, et al. TGF-β: Duality of function between tumor prevention and carcinogenesis. J Natl Cancer Inst. 2014;106(2):djt369. https://doi.org/10.1093/jnci/djt369 PMid:24511106 DOI: https://doi.org/10.1093/jnci/djt369

Sofy MR, Mancy AG, Alnaggar AE, Refaey EE, Mohamed HI, Elnosary ME, et al. A polishing the harmful effects of broad bean mottle virus infecting broad bean plants by enhancing the immunity using different potassium concentrations. Not Bot Horti Agrobot Cluj Napoca. 2022;50(1):12654. https://doi.org/10.15835/nbha50112654 DOI: https://doi.org/10.15835/nbha50112654

Ikeguchi M, Iwamoto A, Taniguchi K, Katano K, Hirooka Y. The gene expression level of transforming growth factor-beta (TGF-beta) as a biological prognostic marker of hepatocellular carcinoma. J Exp Clin Cancer Res. 2005;24(3):415-21. PMid:16270528

Teama S, Fawzy A, Teama S, Helal A, Drwish AD, Elbaz T, et al. Increased serum endoglin and transforming growth factor β1 mRNA expression and risk of hepatocellular carcinoma in cirrhotic Egyptian patients. Asian Pac J Cancer Prev. 2016;17(5):2429-34. PMid:27268609

Peng Q, Chunfang G, Meng F, Qiang J, Yunpeng Z, Yan L, et al. Establishment of a real-time PCR for quantifying transforming growth factor beta1 in blood of hepatocellular carcinoma patients. J Med Coll PLA. 2008;23(4):228-36. https://doi.org/10.1016/S1000-1948(08)60047-7 DOI: https://doi.org/10.1016/S1000-1948(08)60047-7

Dong ZZ, Yao DF, Yao M, Qiu LW, Zong L, Wu W, et al. Clinical impact of plasma TGF-beta1 and circulating TGF-beta1 mRNA in diagnosis of hepatocellular carcinoma. Hepatobiliary Pancreat Dis Int. 2008;7(3):288-95. PMid:18522884

Farid IM, Hamza IM, El-Abd DM, Mohyi AM, AbdulLatif MM, Aref AT, et al. Transforming growth factor-β1 gene expression in hepatocellular carcinoma: A preliminary report. Arab J Gastroenterol. 2014;15(3-4):142-7. https://doi.org/10.1016/j.ajg.2014.10.007 PMid:25475758 DOI: https://doi.org/10.1016/j.ajg.2014.10.007

Lin GH, Wang J, Li SH, Wang J, Xu L, Li SP. Relationship and clinical significance of TGF-beta1 expression with treg cell infiltration in hepatocellular carcinoma. Chin J Cancer. 2010;29(4):403-7. https://doi.org/10.5732/cjc.009.10628 PMid:20346216 DOI: https://doi.org/10.5732/cjc.009.10628

Deng YB, Nagae G, Midorikawa Y, Yagi K, Tsutsumi S, Yamamoto S, et al. Identification of genes preferentially methylated in hepatitis C virus-related hepatocellular carcinoma. Cancer Sci. 2010;101(6):1501-10. https://doi.org/10.1111/j.1349-7006.2010.01549.x PMid:20345479 DOI: https://doi.org/10.1111/j.1349-7006.2010.01549.x

Ciardiello D, Elez E, Tabernero J, Seoane J. Clinical development of therapies targeting TGFβ: Current knowledge and future perspectives. Ann Oncol. 2020;31(10):1336-49. https://doi.org/10.1016/j.annonc.2020.07.009 PMid:32710930 DOI: https://doi.org/10.1016/j.annonc.2020.07.009

Kelley RK, Gane E, Assenat E, Siebler J, Galle PR, Merle P, et al. APhase 2 study of galunisertib (TGF-beta1 receptor Type I inhibitor) and sorafenib in patients with advanced hepatocellular carcinoma. Clin Transl Gastroenterol. 2019;10(7):e00056. https://doi.org/10.14309/ctg.0000000000000056 PMid:31295152 DOI: https://doi.org/10.14309/ctg.0000000000000056