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- C-reactive Protein Overexpression in the Background Liver of Hepatitis B Virus–Associated Hepatocellular Carcinoma Is a Prognostic Biomarker
- Jin Ho Shin, Eunsil Yu, Eun Na Kim, Chong Jai Kim
- J Pathol Transl Med. 2018;52(5):267-274. Published online July 27, 2018
- DOI: https://doi.org/10.4132/jptm.2018.07.14
- 6,165 View
- 171 Download
- 4 Web of Science
- 5 Crossref
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Abstract
PDF - Background
Chronic hepatitis B virus (HBV) infection is a leading cause of hepatocellular carcinoma (HCC). Peripheral blood C-reactive protein (CRP) concentration and CRP overexpression in HCC cells are proven to be prognostic markers for HCC, but the significance of CRP expression in non-neoplastic hepatocytes, which are the primary origin of CRP, has not been studied. This study was conducted to determine the clinicopathologic significance of CRP immunoreactivity in the background liver of HBV-associated HCC.
Methods
CRP immunostaining was done on tissue microarrays of non-neoplastic liver tissues obtained from surgically resected, treatment-naïve HBV-associated HCCs (n = 156). The relationship between CRP immunoreactivity and other clinicopathologic parameters including cancer-specific survival was analyzed. CRP immunoreactivity was determined using a 4-tier grading system: grades 0, 1, 2, and 3.
Results
CRP was positive in 139 of 156 cases (89.1%) of non-neoplastic liver in patients with HCCs: grade 1 in 83 cases (53.2%); grade 2 in 50 cases (32.1%); and grade 3 in six cases (3.8%). The patients with diffuse CRP immunoreactivity (grade 3) had decreased cancer-specific survival (p = .031) and a tendency for shorter interval before early recurrence (p = .050). The degree of CRP immunoreactivity correlated with serum CRP concentration (p < .001).
Conclusions
CRP immunoreactivity in non-neoplastic liver is a novel biomarker for poor cancer-specific survival of HBV-associated HCC and correlates with serum CRP concentration. -
Citations
Citations to this article as recorded by
- Ferritin and procalcitonin serve as discriminative inflammatory biomarkers and can predict the prognosis of severe fever with thrombocytopenia syndrome in its early stages
Keping Chen, Huidi Sun, Yu Geng, Chuankun Yang, Chun Shan, Yuxin Chen
Frontiers in Microbiology.2023;[Epub] CrossRef - Evaluation of Serum Ferritin, Procalcitonin, and C-Reactive Protein for the Prediction of Severity and Mortality in Hemorrhagic Fever With Renal Syndrome
Lihe Che, Zedong Wang, Na Du, Liang Li, Yinghua Zhao, Kaiyu Zhang, Quan Liu
Frontiers in Microbiology.2022;[Epub] CrossRef - Hepatocellular adenomas: recent updates
Haeryoung Kim, Young Nyun Park
Journal of Pathology and Translational Medicine.2021; 55(3): 171. CrossRef - A prospective follow-up study of the relationship between high-sensitivity C-reactive protein and primary liver cancer
Sarah Tan Siyin, Tong Liu, Wenqiang Li, Nan Yao, Guoshuai Xu, Jun Qu, Yajun Chen
BMC Cancer.2020;[Epub] CrossRef - CRP Levels in Viral Hepatitis: A Meta-Analysis Study
Sukhpal Singh, Abhishek Bansal, Pardeep Kumar
International Journal of Infection.2020;[Epub] CrossRef
- Ferritin and procalcitonin serve as discriminative inflammatory biomarkers and can predict the prognosis of severe fever with thrombocytopenia syndrome in its early stages
- Overexpression of C-reactive Protein as a Poor Prognostic Marker of Resectable Hepatocellular Carcinomas
- Jin Ho Shin, Chong Jai Kim, Eun Jeong Jeon, Chang Ohk Sung, Hwa Jeong Shin, Jene Choi, Eunsil Yu
- J Pathol Transl Med. 2015;49(2):105-111. Published online March 12, 2015
- DOI: https://doi.org/10.4132/jptm.2015.01.19
- 10,593 View
- 75 Download
- 20 Web of Science
- 14 Crossref
-
Abstract
PDF
- Background
C-reactive protein (CRP) is an acute phase reactant synthesized in the liver. CRP immunoreactivity is a feature of inflammatory hepatocellular adenomas with a higher risk of malignant transformation. A high serum CRP level denotes poor prognosis in hepatocellular carcinoma (HCC) patients. This study was conducted to determine whether CRP is produced in HCC and to assess the clinicopathologic significance of CRP expression in cancer cells. Methods: CRP immunoreactivity was examined in treatment-naïve HCCs (n=224) using tissue microarrays and was correlated with clinicopathologic parameters. The expression of CRP mRNA and protein was also assessed in 12 HCC cases by quantitative real-time polymerase chain reaction and immunoblotting. Hep3B and SNU-449 HCC cell lines were used for the analysis of CRP mRNA regulation by interleukin 6 (IL-6). Results: CRP was expressed in 133 of 224 HCCs (59.4%) with a variable degree of immunoreactivity (grade 1 in 25.9%; grade 2 in 20.1%; grade 3 in 13.4%). There was an inverse relationship between grade 3 CRP immunoreactivity and cancer-specific survival (p=.0047), while no associations were found with other parameters, including recurrence-free survival. The CRP mRNA expression level was significantly higher in CRP immunopositive cases than in immunonegative cases (p<.05). CRP mRNA expression was increased in Hep3B cells, but was not detected in SNU-449 cells even after IL-6 treatment. Conclusions: We report the expression of CRP in HCC for the first time. CRP expression was associated with poor cancer-specific survival in patients with resectable HCC. -
Citations
Citations to this article as recorded by- Peritumoral portal enhancement during transarterial chemoembolization: a potential prognostic factor for patients with hepatocellular carcinoma
Sofi Sennefelt Nyman, Angeliki Dimopoulou Creusen, Ulf Johnsson, Fredrik Rorsman, Johan Vessby, Charlotte Ebeling Barbier
Acta Radiologica.2022; 63(10): 1323. CrossRef - The quest for precision oncology with immune checkpoint inhibitors for hepatocellular carcinoma
Giuseppe Cabibbo, Amit G. Singal
Journal of Hepatology.2022; 76(2): 262. CrossRef - HNF-1β is a More Sensitive and Specific Marker Than C-Reactive Protein for Identifying Biliary Differentiation in Primary Hepatic Carcinomas
Pallavi A. Patil, Tamar Taddei, Dhanpat Jain, Xuchen Zhang
Archives of Pathology & Laboratory Medicine.2022; 146(2): 220. CrossRef - Malignant transformation of hepatocellular adenoma
Céline Julien, Brigitte Le Bail, Laurence Chiche, Charles Balabaud, Paulette Bioulac-Sage
JHEP Reports.2022; 4(3): 100430. CrossRef - Effect of Treatment with Colchicine after Acute Coronary Syndrome on Major Cardiovascular Events: A Systematic Review and Meta-Analysis of Clinical Trials
Erfan Razavi, Akam Ramezani, Asma Kazemi, Armin Attar, Baohui Xu
Cardiovascular Therapeutics.2022; 2022: 1. CrossRef - Steatotic and Steatohepatitic Hepatocellular Carcinomas
Umut Aykutlu, Asuman Argon, Mehmet Orman, Sezgin Ulukaya, Murat Zeytunlu, Zeki Karasu, Fulya Günşar, Deniz Nart, Ulus Akarca, Funda Yilmaz
American Journal of Surgical Pathology.2021; 45(9): 1252. CrossRef - Cytochrome P450 4A11 expression in tumor cells: A favorable prognostic factor for hepatocellular carcinoma patients
Hyuk Soo Eun, Sang Yeon Cho, Byung Seok Lee, Sup Kim, In‐Sang Song, Kwangsik Chun, Cheong‐Hae Oh, Min‐Kyung Yeo, Seok Hyun Kim, Kyung‐Hee Kim
Journal of Gastroenterology and Hepatology.2019; 34(1): 224. CrossRef - Investigating Trk Protein Expression between Oropharyngeal and Non-oropharyngeal Squamous Cell Carcinoma: Clinical Implications and Possible Roles of Human Papillomavirus Infection
Yoon Ah Cho, Ji Myung Chung, Hyunmi Ryu, Eun Kyung Kim, Byoung Chul Cho, Sun Och Yoon
Cancer Research and Treatment.2019; 51(3): 1052. CrossRef - Increased systemic zonula occludens 1 associated with inflammation and independent biomarker in patients with hepatocellular carcinoma
Amit Kumar Ram, Biju Pottakat, Balasubramaniyan Vairappan
BMC Cancer.2018;[Epub] CrossRef - C-reactive Protein Overexpression in the Background Liver of Hepatitis B Virus–Associated Hepatocellular Carcinoma Is a Prognostic Biomarker
Jin Ho Shin, Eunsil Yu, Eun Na Kim, Chong Jai Kim
Journal of Pathology and Translational Medicine.2018; 52(5): 267. CrossRef - Efficacy of vasopressin V2 receptor antagonist tolvaptan in treatment of hepatic edema
Yasunari Hiramine, Hirofumi Uto, Yasushi Imamura, Takuya Hiwaki, Takeshi Kure, Sho Ijuin, Kohei Oda, Seiichi Mawatari, Kotaro Kumagai, Koki Tokunaga, Hirofumi Higashi, Ichiro Kanetsuki, Osamu Kubozono, Shigeho Maenohara, Akio Ido
Hepatology Research.2017; 47(6): 542. CrossRef - Elevated CRP levels predict poor outcome and tumor recurrence in patients with thymic epithelial tumors: A pro- and retrospective analysis
Stefan Janik, Christine Bekos, Philipp Hacker, Thomas Raunegger, Bahil Ghanim, Elisa Einwallner, Lucian Beer, Walter Klepetko, Leonhard Müllauer, Hendrik J. Ankersmit, Bernhard Moser
Oncotarget.2017; 8(29): 47090. CrossRef - Pretreatment neutrophil-to-lymphocyte ratio predicts prognosis in patients with metastatic renal cell carcinoma receiving targeted therapy
Gui-Ming Zhang, Yao Zhu, Wei-Jie Gu, Hai-Liang Zhang, Guo-Hai Shi, Ding-Wei Ye
International Journal of Clinical Oncology.2016; 21(2): 373. CrossRef - Current Proceedings in the Molecular Dissection of Hepatocellular Adenomas: Review and Hands-on Guide for Diagnosis
Diane Goltz, Hans-Peter Fischer
International Journal of Molecular Sciences.2015; 16(9): 20994. CrossRef
- Peritumoral portal enhancement during transarterial chemoembolization: a potential prognostic factor for patients with hepatocellular carcinoma
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