Angiogenesis, Inflammation & Therapeutics | Online ISSN  2207-872X
RESEARCH ARTICLE   (Open Access)

Combined Biomarkers for Early Diagnosis of Hepatocellular Carcinoma

Tufael 1, Md Mostafizur Rahman 2, Vijay Jagdish Upadhye 3*, Md Faruk Hossain 2, Nasir Uddin 4

+ Author Affiliations

Journal of Angiotherapy 8 (5) 1-12 https://doi.org/10.25163/angiotherapy.859665

Submitted: 31 March 2024 Revised: 06 May 2024  Published: 09 May 2024 


Abstract

Objective: This retrospective study aimed to evaluate the efficacy of serum biomarkers, specifically alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA), and cancer antigen 19-9 (CA19-9), individually and in combination, for screening and diagnosing primary hepatic cancer (PHC) in asymptomatic patients. Methods: A retrospective cross-sectional analysis of 1369 patients from October 2022 to November 2023 was analyzed. Preoperative serum levels of AFP, CEA, and CA19-9 were measured and correlated with histological findings. Sensitivity, specificity, and predictive values were calculated for each biomarker alone and in combination. Results: Patients with PHC exhibited significantly elevated levels of AFP, CEA, and CA19-9 compared to those with liver cirrhosis and healthy controls (P < 0.03). AFP alone showed moderate sensitivity (64.6%) and high specificity (81.7%) for PHC diagnosis. However, combining AFP with CA19-9 and CEA achieved 100% specificity while drastically reducing sensitivity (2.4%). Histological evaluation revealed varying AFP levels across tumor differentiation grades. Conclusion: Despite the elevated levels of CEA and CA19-9 in PHC patients, combining these biomarkers with AFP did not significantly enhance diagnostic accuracy compared to AFP alone. The study suggests that AFP remains a valuable biomarker for screening and diagnosing hepatocellular carcinoma, but further investigations are warranted to explore additional biomarkers or complementary diagnostic modalities for improving early detection and management.

Keywords: Hepatocellular Carcinoma, Serum Biomarkers, Alpha-Fetoprotein, Carcinoembryonic Antigen, Cancer Antigen 19-9.

References


Aghoram, R., Cai, P., Dickinson, J. A., & Cochrane Hepato-Biliary Group. (1996). Alpha-foetoprotein and/or liver ultrasonography for screening of hepatocellular carcinoma in patients with chronic hepatitis B. Cochrane Database of Systematic Reviews, 2012(9).

Ahmadpour, S., & Singh, D. (2019). F18-DCFPyL-PSMA avid biopsy-proven subcutaneous cap-illary haemangioma as a malignancy mimic in the setting of biochemical recurrent prostate carcinoma. Journal of Medical Imaging and Radiation Oncology, 63(S1), 105-151.

Akter, J., Bari, K. F., Salam, M. T., Banik, P. C., Khan, M. S. S., & Sunny, A. R. Significance of Serum      Biomarkers in Early Diagnosis of Hepatocellular Carcinoma in Patient with Fisher Groups.

Akter, J., Bari, K. F., Salam, M. T., Banik, P. C., Khan, M. S. S., & Sunny, A. R. Significance of Serum Biomarkers in Early Diagnosis of Hepatocellular Carcinoma in Patient with Fisher Groups.

Amarapurkar, D., Han, K. H., Chan, H. L. Y., Ueno, Y., & Asia-Pacific Working Party on Prevention of Hepatocellular Carcinoma. (2009). Application of surveillance programs for hepatocellular carcinoma in the Asia–Pacific Region. Journal of gastroenterology and hepatology, 24(6), 955-961.

Bruix, J., & Sherman, M. (2005). Management of hepatocellular carcinoma. Hepatology, 42(5), 1208-1236.

Chen, H., Zhang, Y., Li, S., Li, N., Chen, Y., Zhang, B., ... & Dai, M. (2018). Direct comparison of five serum biomarkers in early diagnosis of hepatocellular carcinoma. Cancer management and research, 1947-1958.

De Stefano, F., Chacon, E., Turcios, L., Marti, F., & Gedaly, R. (2018). Novel biomarkers in hepatocellular carcinoma. Digestive and Liver Disease, 50(11), 1115-1123.

Edoo, M. I. A., Chutturghoon, V. K., Wusu-Ansah, G. K., Hai, Z. H. U., Zhen, T. Y., Xie, H. Y., & Zheng, S. S. (2019). Serum biomarkers AFP, CEA and CA19-9 combined detection for early diagnosis of hepatocellular carcinoma. Iranian journal of public health, 48(2), 314.

El Makarem, M. A. (2012). An overview of biomarkers for the diagnosis of hepatocellular carcinoma. Hepatitis monthly, 12(10 HCC).

El-Serag, H. B., & Kanwal, F. (2014). Epidemiology of hepatocellular carcinoma in the United States: where are we? Where do we go?. Hepatology, 60(5), 1767-1775.

El-Serag, Hashem B., and Fasiha Kanwal. "Epidemiology of hepatocellular carcinoma in the United States: where are we? Where do we go?." Hepatology 60, no. 5 (2014): 1767-1775.

Farinati, F., Marino, D., De Giorgio, M., Baldan, A., Cantarini, M., Cursaro, C., ... & Trevisani, F. (2006). Diagnostic and prognostic role of α-fetoprotein in hepatocellular carcinoma: both or neither?. Official journal of the American College of Gastroenterology| ACG, 101(3), 524-532.

Farrell, G. (2010). Asia-Pacific working party on prevention of hepatocellular carcinoma. Prevention of hepatocellular carcinoma in the Asia-Pacific region: consensus statements. J. Gastroenterol. Hepatol., 25(4), 657.

Forner, A., Gilabert, M., Bruix, J., & Raoul, J. L. (2014). Treatment of intermediate-stage hepatocellular carcinoma. Nature reviews Clinical oncology, 11(9), 525-535.

Johnson, P. J. (2001). The role of serum alpha-fetoprotein estimation in the diagnosis and management of hepatocellular carcinoma. Clinics in liver disease, 5(1), 145-159.

Khien, V. V., Mao, H. V., Chinh, T. T., Ha, P. T., Bang, M. H., Lac, B. V., ... & Satomura, S. (2001). Clinical evaluation of lentil lectin-reactive alpha-fetoprotein-L3 in histology-proven hepatocellular carcinoma. The International journal of biological markers, 16(2), 105-111.

Kudo, M., Han, K. H., Kokudo, N., Cheng, A. L., Choi, B. I., Furuse, J., ... & Sakamoto, M. (2010). Liver cancer working group report. Japanese journal of clinical oncology, 40(suppl_1), i19-i27.

Llovet, J. M., Bustamante, J., Castells, A., Vilana, R., Ayuso, M. D. C., Sala, M., ... & Bruix, J. (1999). Natural history of untreated nonsurgical hepatocellular carcinoma: rationale for the design and evaluation of therapeutic trials. Hepatology, 29(1), 62-67.

Navyatha, B., & Nara, S. (2019). Theranostic nanostructures for ovarian cancer. Critical Reviews™ in Therapeutic Drug Carrier Systems, 36(4).

Oka, H., Tamori, A., Kuroki, T., Kobayashi, K., & Yamamoto, S. (1994). Prospective study of α-fetoprotein in cirrhotic patients monitored for development of hepatocellular carcinoma. Hepatology, 19(1), 61-66.

Sartorius, K., Sartorius, B., Aldous, C., Govender, P. S., & Madiba, T. E. (2015). Global and country underestimation of hepatocellular carcinoma (HCC) in 2012 and its implications. Cancer epidemiology, 39(3), 284-290.

Siegel, R. L., Miller, K. D., & Jemal, A. (2018). Cancer statistics, 2018. CA: a cancer journal for clinicians, 68(1), 7-30.

Singal, A. G., Conjeevaram, H. S., Volk, M. L., Fu, S., Fontana, R. J., Askari, F., ... & Marrero, J. A. (2012). Effectiveness of hepatocellular carcinoma surveillance in patients with cirrhosis. Cancer epidemiology, biomarkers & prevention, 21(5), 793-799.

Singal, A. G., Nehra, M., Adams-Huet, B., Yopp, A. C., Tiro, J. A., Marrero, J. A., ... & Lee, W. M. (2013). Detection of hepatocellular carcinoma at advanced stages among patients in the HALT-C trial: where did surveillance fail?. Official journal of the American College of Gastroenterology| ACG, 108(3), 425-432.

Song, P., Feng, X., Zhang, K., Song, T., Ma, K., Kokudo, N., ... & Tang, W. (2013). Perspectives on using des-γ-carboxyprothrombin (DCP) as a serum biomarker: facilitating early detection of hepatocellular carcinoma in China. Hepatobiliary surgery and nutrition, 2(4), 227.

Song, P., Feng, X., Zhang, K., Song, T., Ma, K., Kokudo, N., ... & Tang, W. (2013). Screening for and surveillance of high-risk patients with HBV-related chronic liver disease: promoting the early detection of hepatocellular carcinoma in China. Bioscience trends, 7(1), 1-6.

Song, P., Gao, J., Inagaki, Y., Kokudo, N., Hasegawa, K., Sugawara, Y., & Tang, W. (2013). Biomarkers: evaluation of screening for and early diagnosis of hepatocellular carcinoma in Japan and China. Liver cancer, 2(1), 31-39.

Song, P., Gao, J., Inagaki, Y., Kokudo, N., Hasegawa, K., Sugawara, Y., & Tang, W. (2013). Biomarkers: evaluation of screening for and early diagnosis of hepatocellular carcinoma in Japan and China. Liver cancer, 2(1), 31-39.

Song, P., Tang, Q., Feng, X., & Tang, W. (2016). Biomarkers: evaluation of clinical utility in surveillance and early diagnosis for hepatocellular carcinoma. Scandinavian Journal of Clinical and Laboratory Investigation, 76(sup245), S70-S76.

Song, P., Tobe, R. G., Inagaki, Y., Kokudo, N., Hasegawa, K., Sugawara, Y., & Tang, W. (2012). The management of hepatocellular carcinoma around the world: a comparison of guidelines from 2001 to 2011. Liver International, 32(7), 1053-1063.

Tanaka, M., Katayama, F., Kato, H., Tanaka, H., Wang, J., Qiao, Y. L., & Inoue, M. (2011). Hepatitis B and C virus infection and hepatocellular carcinoma in China: a review of epidemiology and control measures. Journal of epidemiology, 21(6), 401-416.

Torre, L. A., Bray, F., Siegel, R. L., Ferlay, J., Lortet-Tieulent, J., & Jemal, A. (2015). Global cancer statistics, 2012. CA: a cancer journal for clinicians, 65(2), 87-108.

Trevisani, F., D'Intino, P. E., Morselli-Labate, A. M., Mazzella, G., Accogli, E., Caraceni, P., ... & Bernardi, M. (2001). Serum α-fetoprotein for diagnosis of hepatocellular carcinoma in patients with chronic liver disease: influence of HBsAg and anti-HCV status. Journal of hepatology, 34(4), 570-575.

Tsuchiya, N., Sawada, Y., Endo, I., Saito, K., Uemura, Y., & Nakatsura, T. (2015). Biomarkers for the early diagnosis of hepatocellular carcinoma. World journal of gastroenterology: WJG, 21(37), 10573.

Tufael, M., Upadhye, V. J., Sunny, A. R., Raposo, A., Islam, M. S., Rashid, M. H. O., ... & Rahman, M. M. (2024). Correlation Between Tumor Differentiation and Biomarkers in Hepatocellular Carcinoma: Implications for Early Diagnosis and Treatment.

Wang, M., Singal, A. G., Parikh, N., Kono, Y., Marrero, J., & Mehta, A. (2022). A Biomarker Panel Based upon AFP, Fucosylated Kininogen and PEG-Precipitated IgG Is Highly Accurate for the Early Detection Hepatocellular Carcinoma in Patients with Cirrhosis in Phase II and Phase III Biomarker Evaluation. Cancers, 14(23), 5970.

Williams, J., & Stebbing, J. (2021). COVID-19 and the risk to cancer patients in China. International Journal of Cancer, 148(2), 265.

Xu, T. (2015). Chinese Anti-Cancer Association as a non-governmental organization undertakes systematic cancer prevention work in China. Chinese Journal of Cancer Research, 27(4), 423.

Yoshida, S., Kurokohchi, K. A. Z. U. T. A. K. A., Arima, K., Masaki, T., Hosomi, N. A. O. K. I., Funaki, T., ... & Kuriyama, S. (2002). Clinical significance of lens culinaris agglutinin-reactive fraction of serum α-fetoprotein in patients with hepatocellular carcinoma. International journal of oncology, 20(2), 305-309.

Zhang, C., Zhong, Y., & Guo, L. (2013). Strategies to prevent hepatitis B virus infection in China: immunization, screening, and standard medical practices. Bioscience trends, 7(1), 7-12.

Zheng, Y., Yu, K., Du, J., Jiang, L., Zhang, S., Han, Y., ... & Tan, Y. (2010). Potential therapeutic strategy for non-Hodgkin lymphoma by anti-CD20scFvFc/CD28/CD3zeta gene tranfected T cells. Journal of Experimental & Clinical Cancer Research, 29, 1-8.

Zoli, M., Magalotti, D., Bianchi, G., Gueli, C., Marchesini, G., & Pisi, E. (1996). Efficacy of a surveillance program for early detection of hepatocellular carcinoma. Cancer: Interdisciplinary International Journal of the American Cancer Society, 78(5), 977-985.

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