Login Register Cart 0
Generic placeholder image

Current Cancer Drug Targets

Editor-in-Chief

ISSN (Print): 1568-0096
ISSN (Online): 1873-5576

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

Establishment and Validation of a Blood Test-based Nomogram to Diagnose Patients with AFP-negative HCC

Author(s): Yujing Wu*, Shuang Liu*, Zhijuan Fan, Yaqiong Tian, Lei Zhang and Shuye Liu

Volume 24, Issue 5, 2024

Published on: 03 January, 2024

Page: [556 - 564] Pages: 9

DOI: 10.2174/0115680096264770231113103930

Price: $65

Abstract

Background: Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer death worldwide. Alpha-protein (AFP) is the most widely used blood biomarker for HCC. However, elevated serum AFP is only observed in part of HCC.

Aims: This study aimed to develop an efficient nomogram model to distinguish patients with alpha- protein-negative HCC and liver cirrhosis.

Objectives: A total of 1130 patients (508 HCC patients + 622 cirrhosis patients) were enrolled in the training cohort. A total of 244 HCC patients and 246 cirrhosis patients were enrolled in the validation cohort.

Methods: A total of 41 parameters about blood tests were analyzed with logistic regression. The nomogram was based on independent factors and validated both internally and externally.

Results: Independent factors were eosinophils %, hemoglobin concentration distribution width, fibrinogen, platelet counts, total bile acid, and mitochondria aspartate aminotransferase. The calibration curve for the probability of HCC showed good agreement between prediction by nomogram and actual observation. The concordance index was 0.851. In the validation cohort, the nomogram distinguished HCC from liver cirrhosis with an area under the curve of receiver operating characteristic of 0.754.

Conclusion: This proposed nomogram was an accurate and useful method to distinguish patients with AFP-negative HCC from liver cirrhosis.

« Previous Next »
Graphical Abstract

[1]
Yang, J.D.; Hainaut, P.; Gores, G.J.; Amadou, A.; Plymoth, A.; Roberts, L.R. A global view of hepatocellular carcinoma: Trends, risk, prevention and management. Nat. Rev. Gastroenterol. Hepatol., 2019, 16(10), 589-604.
[http://dx.doi.org/10.1038/s41575-019-0186-y] [PMID: 31439937]
[2]
Chidambaranathan-Reghupaty, S.; Fisher, P.B.; Sarkar, D. Hepatocellular carcinoma (HCC): Epidemiology, etiology and molecular classification. Adv. Cancer Res., 2021, 149, 1-61.
[http://dx.doi.org/10.1016/bs.acr.2020.10.001] [PMID: 33579421]
[3]
Fasolato, S.; Pigozzo, S.; Pontisso, P.; Angeli, P.; Ruscica, M.; Savarino, E.; De Martin, S.; Lupo, M.G.; Ferri, N. PCSK9 levels are raised in chronic HCV patients with hepatocellular carcinoma. J. Clin. Med., 2020, 9(10), 3134.
[http://dx.doi.org/10.3390/jcm9103134] [PMID: 32998342]
[4]
Wiciński, M.; Żak, J.; Malinowski, B.; Popek, G.; Grześk, G. PCSK9 signaling pathways and their potential importance in clinical practice. EPMA J., 2017, 8(4), 391-402.
[http://dx.doi.org/10.1007/s13167-017-0106-6] [PMID: 29209441]
[5]
Moudi, B.; Heidari, Z.; Mahmoudzadeh-Sagheb, H.; Alavian, S.M.; Lankarani, K.B.; Farrokh, P.; Randel Nyengaard, J. Concomitant use of heat-shock protein 70, glutamine synthetase and glypican-3 is useful in diagnosis of HBV-related hepatocellular carcinoma with higher specificity and sensitivity. Eur. J. Histochem., 2018, 62(1), 2859.
[http://dx.doi.org/10.4081/ejh.2018.2859] [PMID: 29569872]
[6]
Chan, H.L.Y.; Vogel, A.; Berg, T.; De Toni, E.N.; Kudo, M.; Trojan, J.; Eiblmaier, A.; Klein, H.G.; Hegel, J.K.; Sharma, A.; Madin, K.; Rolny, V.; Lisy, M.R.; Piratvisuth, T. Performance evaluation of the Elecsys PIVKA-II and Elecsys AFP assays for hepatocellular carcinoma diagnosis. JGH Open, 2022, 6(5), 292-300.
[http://dx.doi.org/10.1002/jgh3.12720] [PMID: 35601131]
[7]
Su, T.H.; Peng, C.Y.; Chang, S.H.; Tseng, T.C.; Liu, C.J.; Chen, C.L.; Liu, C.H.; Yang, H.C.; Chen, P.J.; Kao, J.H. Serum PIVKA-II and alpha-fetoprotein at virological remission predicts hepatocellular carcinoma in chronic hepatitis B related cirrhosis. J. Formos. Med. Assoc., 2022, 121(3), 703-711.
[http://dx.doi.org/10.1016/j.jfma.2021.08.003] [PMID: 34452785]
[8]
Piratvisuth, T.; Tanwandee, T.; Thongsawat, S.; Sukeepaisarnjaroen, W.; Esteban, J.I.; Bes, M.; Köhler, B.; He, Y.; Swiatek-de Lange, M.; Morgenstern, D.; Chan, H.L.Y. Multimarker panels for detection of early stage hepatocellular carcinoma: A prospective, multicenter, case-control study. Hepatol. Commun., 2022, 6(4), 679-691.
[http://dx.doi.org/10.1002/hep4.1847] [PMID: 34796691]
[9]
Marrero, J.A.; Kulik, L.M.; Sirlin, C.B.; Zhu, A.X.; Finn, R.S.; Abecassis, M.M.; Roberts, L.R.; Heimbach, J.K. Diagnosis, staging, and management of hepatocellular carcinoma: 2018 practice guidance by the american association for the study of liver diseases. Hepatology, 2018, 68(2), 723-750.
[http://dx.doi.org/10.1002/hep.29913] [PMID: 29624699]
[10]
Galle, P.R.; Forner, A.; Llovet, J.M.; Mazzaferro, V.; Piscaglia, F.; Raoul, J-L.; Schirmacher, P.; Vilgrain, V. Management of hepatocellular carcinoma. J. Hepatol., 2018, 69(1), 182-236.
[http://dx.doi.org/10.1016/j.jhep.2018.03.019] [PMID: 29628281]
[11]
Pepe, M.S.; Etzioni, R.; Feng, Z.; Potter, J.D.; Thompson, M.L.; Thornquist, M.; Winget, M.; Yasui, Y. Phases of biomarker development for early detection of cancer. J. Natl. Cancer Inst., 2001, 93(14), 1054-1061.
[http://dx.doi.org/10.1093/jnci/93.14.1054] [PMID: 11459866]
[12]
Singal, A.G.; Hoshida, Y.; Pinato, D.J.; Marrero, J.; Nault, J.C.; Paradis, V.; Tayob, N.; Sherman, M.; Lim, Y.S.; Feng, Z.; Lok, A.S.; Rinaudo, J.A.; Srivastava, S.; Llovet, J.M.; Villanueva, A. International liver cancer association (ILCA) white paper on biomarker development for hepatocellular carcinoma. Gastroenterology, 2021, 160(7), 2572-2584.
[http://dx.doi.org/10.1053/j.gastro.2021.01.233] [PMID: 33705745]
[13]
Parikh, N.D.; Tayob, N.; Singal, A.G. Blood-based biomarkers for hepatocellular carcinoma screening: Approaching the end of the ultrasound era? J. Hepatol., 2023, 78(1), 207-216.
[http://dx.doi.org/10.1016/j.jhep.2022.08.036] [PMID: 36089157]
[14]
She, S.; Xiang, Y.; Yang, M.; Ding, X.; Liu, X.; Ma, L.; Liu, Q.; Liu, B.; Lu, Z.; Li, S.; Liu, Y.; Ran, X.; Xu, X.; Hu, H.; Hu, P.; Zhang, D.; Ren, H.; Yang, Y. C-reactive protein is a biomarker of AFP-negative HBV-related hepatocellular carcinoma. Int. J. Oncol., 2015, 47(2), 543-554.
[http://dx.doi.org/10.3892/ijo.2015.3042] [PMID: 26058824]
[15]
Hu, J.; Li, H.; Li, T.; Liu, J. A nomogram to predict microvascular invasion in early hepatocellular carcinoma. J. Cancer Res. Ther., 2021, 17(3), 652-657.
[http://dx.doi.org/10.4103/jcrt.JCRT_1714_20] [PMID: 34269295]
[16]
Mao, S.; Yu, X.; Shan, Y.; Fan, R.; Wu, S.; Lu, C. Albumin-bilirubin (ALBI) and monocyte to lymphocyte ratio (MLR)-based nomogram model to predict tumor recurrence of AFP-negative hepatocellular carcinoma. J. Hepatocell. Carcinoma, 2021, 8, 1355-1365.
[http://dx.doi.org/10.2147/JHC.S339707] [PMID: 34805014]
[17]
Yang, L.; Gu, D.; Wei, J.; Yang, C.; Rao, S.; Wang, W.; Chen, C.; Ding, Y.; Tian, J.; Zeng, M. A radiomics nomogram for preoperative prediction of microvascular invasion in hepatocellular carcinoma. Liver Cancer, 2019, 8(5), 373-386.
[http://dx.doi.org/10.1159/000494099] [PMID: 31768346]
[18]
Medical administration of the national health care commission of the People’s Republic of China. Guideline for diagnosing and treatment of primary liver cancer (2019 edition). Chin J Prac Surg, 2020, 40(2), 121-138.
[19]
Chinese society of hepatology, chinese medical association. Chinese guidelines on the management of liver cirrhosis. Zhonghua Gan Zang Bing Za Zhi, 2019, 27(11), 846-865.
[PMID: 31941240]
[20]
Schwabe, R.F.; Tabas, I.; Pajvani, U.B. Mechanisms of fibrosis development in nonalcoholic steatohepatitis. Gastroenterology, 2020, 158(7), 1913-1928.
[http://dx.doi.org/10.1053/j.gastro.2019.11.311] [PMID: 32044315]
[21]
Ramachandran, P.; Matchett, K.P.; Dobie, R.; Wilson-Kanamori, J.R.; Henderson, N.C. Single-cell technologies in hepatology: New insights into liver biology and disease pathogenesis. Nat. Rev. Gastroenterol. Hepatol., 2020, 17(8), 457-472.
[http://dx.doi.org/10.1038/s41575-020-0304-x] [PMID: 32483353]
[22]
Li, G.; Hu, H.; Shi, W.; Li, Y.; Liu, L.; Chen, Y.; Hu, X.; Wang, J.; Gao, J.; Yin, D. Elevated hematocrit in nonalcoholic fatty liver disease: A potential cause for the increased risk of cardiovascular disease? Clin. Hemorheol. Microcirc., 2012, 51(1), 59-68.
[http://dx.doi.org/10.3233/CH-2011-1509] [PMID: 22240370]
[23]
Varricchi, G.; Galdiero, M.R.; Loffredo, S.; Lucarini, V.; Marone, G.; Mattei, F.; Marone, G.; Schiavoni, G. Eosinophils: The unsung heroes in cancer? OncoImmunology, 2018, 7(2), e1393134.
[http://dx.doi.org/10.1080/2162402X.2017.1393134] [PMID: 29308325]
[24]
Reichman, H.; Itan, M.; Rozenberg, P.; Yarmolovski, T.; Brazowski, E.; Varol, C.; Gluck, N.; Shapira, S.; Arber, N.; Qimron, U.; Karo-Atar, D.; Lee, J.J.; Munitz, A. Activated eosinophils exert antitumorigenic activities in colorectal cancer. Cancer Immunol. Res., 2019, 7(3), 388-400.
[http://dx.doi.org/10.1158/2326-6066.CIR-18-0494] [PMID: 30665890]
[25]
Kwon, H.J.; Lee, S.; Lee, H.H.; Cho, H.; Jung, J. Korean red ginseng enhances immunotherapeutic effects of NK cells via eosinophils in metastatic liver cancer model. Nutrients, 2021, 14(1), 134.
[http://dx.doi.org/10.3390/nu14010134] [PMID: 35011007]
[26]
Midorikawa, Y.; Takayama, T.; Higaki, T.; Aramaki, O.; Teramoto, K.; Yoshida, N.; Tsuji, S.; Kanda, T.; Moriyama, M. High platelet count as a poor prognostic factor for liver cancer patients without cirrhosis. Biosci. Trends, 2020, 14(5), 368-375.
[http://dx.doi.org/10.5582/bst.2020.03230] [PMID: 32713867]
[27]
Padickakudy, R.; Pereyra, D.; Offensperger, F.; Jonas, P.; Oehlberger, L.; Schwarz, C.; Haegele, S.; Assinger, A.; Brostjan, C.; Gruenberger, T.; Starlinger, P. Bivalent role of intra-platelet serotonin in liver regeneration and tumor recurrence in humans. J. Hepatol., 2017, 67(6), 1243-1252.
[http://dx.doi.org/10.1016/j.jhep.2017.08.009] [PMID: 28842294]
[28]
Lisman, T.; Porte, R.J. Mechanisms of platelet-mediated liver regeneration. Blood, 2016, 128(5), 625-629.
[http://dx.doi.org/10.1182/blood-2016-04-692665] [PMID: 27297793]
[29]
Guo, C.; Liang, H.; Yuan, W.; Qin, Y. Analysis on the value of soluble intercellular adhesion molecule-1 (sICAM-1), alpha fetoprotein (AFP), and aspartate aminotransferase/platelet ratio index (APRI) in predicting the prognostic survival of patients with primary liver cancer after radiofrequency ablation. Ann. Palliat. Med., 2021, 10(4), 4760-4767.
[http://dx.doi.org/10.21037/apm-21-749] [PMID: 33966425]
[30]
Jansen, P.L.M. Endogenous bile acids as carcinogens. J. Hepatol., 2007, 47(3), 434-435.
[http://dx.doi.org/10.1016/j.jhep.2007.06.001] [PMID: 17624466]
[31]
Gao, L.; Lv, G.; Li, R.; Liu, W.; Zong, C.; Ye, F.; Li, X.; Yang, X.; Jiang, J.; Hou, X.; Jing, Y.; Han, Z.; Wei, L. Glycochenodeoxycholate promotes hepatocellular carcinoma invasion and migration by AMPK/mTOR dependent autophagy activation. Cancer Lett., 2019, 454, 215-223.
[http://dx.doi.org/10.1016/j.canlet.2019.04.009] [PMID: 30980867]
[32]
Wang, T.; Zhang, K.H. New blood biomarkers for the diagnosis of AFP-negative hepatocellular carcinoma. Front. Oncol., 2020, 10, 1316.
[http://dx.doi.org/10.3389/fonc.2020.01316] [PMID: 32923383]
[33]
Lai, Y.C.; Ushio, N.; Rahman, M.M.; Katanoda, Y.; Ogihara, K.; Naya, Y.; Moriyama, A.; Iwanaga, T.; Saitoh, Y.; Sogawa, T.; Sunaga, T.; Momoi, Y.; Izumi, H.; Miyoshi, N.; Endo, Y.; Fujiki, M.; Kawaguchi, H.; Miura, N. Aberrant expression of microRNAs and the miR-1/MET pathway in canine hepatocellular carcinoma. Vet. Comp. Oncol., 2018, 16(2), 288-296.
[http://dx.doi.org/10.1111/vco.12379] [PMID: 29314614]
[34]
Shi, M.; Jiang, Y.; Yang, L.; Yan, S.; Wang, Y.G.; Lu, X.J. Decreased levels of serum exosomal miR-638 predict poor prognosis in hepatocellular carcinoma. J. Cell. Biochem., 2018, 119(6), 4711-4716.
[http://dx.doi.org/10.1002/jcb.26650] [PMID: 29278659]
[35]
Xiong, Y.; Xie, C.R.; Zhang, S.; Chen, J.; Yin, Z.Y. Detection of a novel panel of somatic mutations in plasma cell-free DNA and its diagnostic value in hepatocellular carcinoma. Cancer Manag. Res., 2019, 11, 5745-5756.
[http://dx.doi.org/10.2147/CMAR.S197455] [PMID: 31303788]
[36]
Lyra-González, I.; Flores-Fong, L.E.; González-García, I.; Medina-Preciado, D.; Armendáriz-Borunda, J. MicroRNAs dysregulation in hepatocellular carcinoma: Insights in genomic medicine. World J. Hepatol., 2015, 7(11), 1530-1540.
[http://dx.doi.org/10.4254/wjh.v7.i11.1530] [PMID: 26085912]
[37]
Wu, X.M.; Xi, Z.F.; Liao, P.; Huang, H.D.; Huang, X.Y.; Wang, C.; Ma, Y.; Xia, Q.; Yao, J.G.; Long, X.D. Diagnostic and prognostic potential of serum microRNA-4651 for patients with hepatocellular carcinoma related to aflatoxin B1. Oncotarget, 2017, 8(46), 81235-81249.
[http://dx.doi.org/10.18632/oncotarget.16027] [PMID: 29113383]
[38]
Lin, X.J.; Chong, Y.; Guo, Z.W.; Xie, C.; Yang, X.J.; Zhang, Q.; Li, S.P.; Xiong, Y.; Yuan, Y.; Min, J.; Jia, W.H.; Jie, Y.; Chen, M.S.; Chen, M.X.; Fang, J.H.; Zeng, C.; Zhang, Y.; Guo, R.P.; Wu, Y.; Lin, G.; Zheng, L.; Zhuang, S.M. A serum microRNA classifier for early detection of hepatocellular carcinoma: A multicentre, retrospective, longitudinal biomarker identification study with a nested case-control study. Lancet Oncol., 2015, 16(7), 804-815.
[http://dx.doi.org/10.1016/S1470-2045(15)00048-0] [PMID: 26088272]
[39]
Zuo, D.; Chen, L.; Liu, X.; Wang, X.; Xi, Q.; Luo, Y.; Zhang, N.; Guo, H. Combination of miR-125b and miR-27a enhances sensitivity and specificity of AFP-based diagnosis of hepatocellular carcinoma. Tumour Biol., 2016, 37(5), 6539-6549.
[http://dx.doi.org/10.1007/s13277-015-4545-1] [PMID: 26637228]
[40]
Jing, W.; Peng, R.; Zhu, M.; Lv, S.; Jiang, S.; Ma, J.; Ming, L. Differential expression and diagnostic significance of pre-albumin, fibrinogen combined with D-Dimer in AFP-negative hepatocellular carcinoma. Pathol. Oncol. Res., 2020, 26(3), 1669-1676.
[http://dx.doi.org/10.1007/s12253-019-00752-8] [PMID: 31578661]
[41]
Kong, C.; Zhao, Z.; Chen, W.; Lv, X.; Shu, G.; Ye, M.; Song, J.; Ying, X.; Weng, Q.; Weng, W.; Fang, S.; Chen, M.; Tu, J.; Ji, J. Prediction of tumor response via a pretreatment MRI radiomics-based nomogram in HCC treated with TACE. Eur. Radiol., 2021, 31(10), 7500-7511.
[http://dx.doi.org/10.1007/s00330-021-07910-0] [PMID: 33860832]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy