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Clinicopathological and Prognostic Implications of Arginase Expression in Hepatocellular Carcinoma

Mao, Huahui; Weili, Gao; Lu, Guo-chun; Fang, Fu Min; Teng, Lisong

doi:10.7754/clin.lab.2012.120210

Cited by 11 publications

(10 citation statements)

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“…The prognostic significance of arginase-1 has only been analyzed in one study to date. Mao and colleagues [8] showed that high arginase-1 expression was associated with higher recurrence-free and overall survival. However, 98% of the HCC tumors in that study showed arginase-1 expression, as detected by immunostaining with a polyclonal antibody, which may have increased nonspecific staining, making clear stratification of arginase-1 expression hard to interpret.…”

Section: Discussionmentioning

confidence: 99%

“…The prognostic value of arginase-1 has only been analyzed in one study to date. Mao and colleagues [8] showed that high arginase-1 expression was associated with better recurrence-free and overall survival; however, their stratification of patients into high and low arginase expression was not clearly elucidated, since 98% of all the HCC tumors examined expressed arginase-1.…”

Section: Introductionmentioning

confidence: 99%

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Prognostic Implications of Arginase and Cytokeratin 19 Expression in Hepatocellular Carcinoma After Curative Hepatectomy: Correlation With Recurrence-Free Survival

Obiorah

Chahine

et al. 2019

Gastroenterol Res

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Background The prognostic value of arginase expression in hepatocellular carcinoma (HCC) has been evaluated previously. However, no clear distinction exists yet on the role of arginase-1 as a predictor of recurrence in HCC. Cytokeratin 19 (CK19), a cholangiocytic marker, is occasionally expressed in HCC, but the combination of arginase-1 and CK19 expression has never been evaluated. The aim of the study was to investigate the usefulness of arginase-1 and CK19 expression alone and in combination for prognosticating HCC tumor recurrence after surgical resection. Methods Tissue sections from 112 HCCs were immunostained using an automated method and the mouse monoclonal arginase-1 and mouse monoclonal CK19 antibodies. The clinicopathologic variables, including alpha-fetoprotein levels, viral hepatitis, cirrhosis, tumor size, grade and number, vascular invasion, tumor-node-metastasis (TNM) stage, and tumor recurrence and survival, were obtained from each patient’s medical records. The variables were assessed for correlation with the immunochemical results. Comparisons of recurrence-free and overall survival were performed using univariate and multivariate regression analyses. A P-value of ≤ 0.05 was considered statistically significant. Results High arginase-1 expression was detected in the HCCs of 93 patients (83%), whereas CK19 was positive in the HCCs of only 19 patients (17%). In the univariate analyses, CK19 positivity in HCC was associated with decreased recurrence-free survival compared with CK19-negative HCC (P = 0.0002). Arginase-1 expression was associated with decreased recurrence-free survival when patients were stratified over advanced TNM stage and presence of vascular invasion. The combination of arginase-1 and CK19 expression was a better predictor of decreased recurrence-free survival (P = 0.00008). Arginase-1/CK19 expressions when combined with multiple tumors, TNM stage and vascular invasion were also associated with decreased recurrence-free survival. In the multivariate analysis, tumor grade, CK19 and arginase-1/CK19 expressions were identified as independent prognostic indicators for decreased recurrence-free survival. Conclusion Arginase-1 and CK19 combination immunoreactivity is a potential biomarker of adverse prognosis in HCC, correlating with the presence of multiple tumors, vascular invasion and advanced stage.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Prognostic Implications of Arginase and Cytokeratin 19 Expression in Hepatocellular Carcinoma After Curative Hepatectomy: Correlation With Recurrence-Free Survival

Obiorah

Chahine

et al. 2019

Gastroenterol Res

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“…Reports on the pathological significance of Arg-1 expression in liver cancer cells are limited in number. To date, only a single report has been found in the literature research 8. According to this report, high Arg-1 expression in HCC cells is significantly associated with less aggressive clinicopathological factors, such as less portal vein invasion, less microvessel invasion, lower TNM stage and lower histological grade 8.…”

Section: Discussionmentioning

confidence: 94%

“…To date, only a single report has been found in the literature research 8. According to this report, high Arg-1 expression in HCC cells is significantly associated with less aggressive clinicopathological factors, such as less portal vein invasion, less microvessel invasion, lower TNM stage and lower histological grade 8. Thus, high expression of Arg-1 in tumour cells of HCC and CHC-INT could be associated with less aggressive behaviour although the precise mechanisms still remain elusive.…”

Section: Discussionmentioning

confidence: 99%

The expression of arginase-1, keratin (K) 8 and K18 in combined hepatocellular-cholangiocarcinoma, subtypes with stem-cell features, intermediate-cell type

et al. 2016

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“…Increased arginase expression and activity have been reported in many tumors, such as head and neck, kidney, breast, hepatocellular, and prostate [28,54,[75][76][77]. In fact, in prostatic diseases, arginine metabolism and arginase activity arise as natural subjects of interest since arginase expression and polyamine synthesis were found to be elevated in prostate cancer and associated with differentiation [13,28,50,[78][79][80].…”

Section: Arginine Metabolism In Prostate Cancer Tumorsmentioning

confidence: 99%

Arginine and Arginases Modulate Metabolism, Tumor Microenvironment and Prostate Cancer Progression

et al. 2021

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Arginine availability and activation of arginine-related pathways at cancer sites have profound effects on the tumor microenvironment, far beyond their well-known role in the hepatic urea cycle. Arginine metabolism impacts not only malignant cells but also the surrounding immune cells behavior, modulating growth, survival, and immunosurveillance mechanisms, either through an arginase-mediated effect on polyamines and proline synthesis, or by the arginine/nitric oxide pathway in tumor cells, antitumor T-cells, myeloid-derived suppressor cells, and macrophages. This review presents evidence concerning the impact of arginine metabolism and arginase activity in the prostate cancer microenvironment, highlighting the recent advances in immunotherapy, which might be relevant for prostate cancer. Even though further research is required, arginine deprivation may represent a novel antimetabolite strategy for the treatment of arginine-dependent prostate cancer.

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Clinicopathological and Prognostic Implications of Arginase Expression in Hepatocellular Carcinoma

Cited by 11 publications

References 0 publications

Prognostic Implications of Arginase and Cytokeratin 19 Expression in Hepatocellular Carcinoma After Curative Hepatectomy: Correlation With Recurrence-Free Survival

Prognostic Implications of Arginase and Cytokeratin 19 Expression in Hepatocellular Carcinoma After Curative Hepatectomy: Correlation With Recurrence-Free Survival

The expression of arginase-1, keratin (K) 8 and K18 in combined hepatocellular-cholangiocarcinoma, subtypes with stem-cell features, intermediate-cell type

Arginine and Arginases Modulate Metabolism, Tumor Microenvironment and Prostate Cancer Progression

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