Dear Editor,
Hepatocellular carcinoma (HCC) is a common primary liver malignancy worldwide with a poor prognosis (1) and is the third leading cause of cancer - related deaths (2).
Chronic hepatitis B (HBV) infection, which can cause liver inflammation, has been seen in many individuals with HCC. In addition, fibrosis and cirrhosis are inevitable complications of the infection, which leads to the death of a patient (3, 4).
Early diagnosis of this can prevent the death of a patient and is a crucial factor in the treatment process (5).
It seems that urea cycle enzymes are reliable marker for hepatocytes. For example, arginase - 1 (Arg - 1), which mainly concentrates in periportal hepatocytes (6), is one of the urea cycle enzymes that is expressed in a healthy liver (7).
Chrzanowska et al., assessed Arg - 1 expression by advanced PCR methods and found decreased expression of Arg - 1 in cirrhotic nodules and HCCs (8).
Recently, we found that the expressions of Arg - 1 significantly reduced in patients with HBV - related HCC compared to the patients with only HBV, which can probably manage the diagnosis process of HCC in a way that is time - consuming. The specificity of Arg - 1, among all groups we tested, was 88.4%. Our data emphasized that Arg - 1 can be one of the best markers for HCC on fine - needle aspiration specimens. The results of this study will be released. We also reported Arg - 1 as a very sensitive marker for hepatocytes, which supports Benjamin et al., conclusion as well (9).
Benjamin et al., (9) found the overall sensitivity to be about 96.0% for Arg - 1 in hepatocytes and hepatocellular neoplasms. In addition, all HCCs in their study were reactive for Arg - 1. Moreover, the study of nonhepatocellular tumors revealed that only 2 non - HCC tumors were reactive for Arg - 1.
Furthermore, proper combination of Arg - 1, with some reliable biomarkers such as HepPar - 1 could increase the specificity, accuracy, and precision of natural history of HBV - related HCC diagnosis. We proposed an algorithm to study the natural history of HCC using 2 markers of malignancy (HepPar - 1 and Arg - 1) and found that the respective specificity of Arg - 1 + HepPar - 1 is 100% when we examined HCC cases that were infected previously with HBV.
In another study, Timek et al., (10) performed a triplet algorithm including Arg - 1, hepatocyte paraffin - 1 (HepPar1), and glypican - 3 on liver specimens. They showed that none of the nonhepatic tumor cases were positive for Arg - 1. A total of 19 HCCs samples responded to all three markers, 9 samples responded with only 1 or 2 markers and only 1 case was negative for all 3 markers. Timek suggested the use of 3 markers in differentiating between HCC and metastatic carcinoma.
In conclusion, most of the Arg - 1 studies demonstrated that Arg - 1 has a high sensitivity and specificity in diagnosis of HBV - related HCC and it seems that Arg - 1 can probably be used in detecting HBV infected patients, which are susceptible to HCC. Arg - 1 can develop as an identifier biomarker in pathology of HCC. In addition, the proper combination of Arg - 1 and some well - known and reliable biomarkers is more effective in the study of natural history of the liver malignancy in different stages.
References
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1.
Moudi B, Heidari Z, Mahmoudzadeh-Sagheb H, Alavian SM, Lankarani KB, Farrokh P, et al. 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. [PubMed ID: 29569872]. [PubMed Central ID: PMC5806503]. https://doi.org/10.4081/ejh.2018.2859.
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Li H, Wang S, Wang G, Zhang Z, Wu X, Zhang T, et al. Yes-associated protein expression is a predictive marker for recurrence of hepatocellular carcinoma after liver transplantation. Dig Surg. 2014;31(6):468-78. [PubMed ID: 25632982]. https://doi.org/10.1159/000370252.
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Chrzanowska A, Gajewska B, Baranczyk-Kuzma A. Arginase isoenzymes in human cirrhotic liver. Acta Biochim Pol. 2009;56(3):465-9. [PubMed ID: 19636440].
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Yan BC, Gong C, Song J, Krausz T, Tretiakova M, Hyjek E, et al. Arginase-1: a new immunohistochemical marker of hepatocytes and hepatocellular neoplasms. Am J Surg Pathol. 2010;34(8):1147-54. [PubMed ID: 20661013]. [PubMed Central ID: PMC3160135]. https://doi.org/10.1097/PAS.0b013e3181e5dffa.
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Timek DT, Shi J, Liu H, Lin F. Arginase-1, HepPar-1, and Glypican-3 are the most effective panel of markers in distinguishing hepatocellular carcinoma from metastatic tumor on fine-needle aspiration specimens. Am J Clin Pathol. 2012;138(2):203-10. [PubMed ID: 22904131]. https://doi.org/10.1309/AJCPK1ZC9WNHCCMU.