Abnormal expression of HNRNPA3 in multistep hepatocarcinogenesis

Ren,Xinlu; Dong,Yi; Duan,Miao; Zhang,Hui; Gao,Peng

doi:10.3892/ol.2020.12307

Abnormal expression of HNRNPA3 in multistep hepatocarcinogenesis

Authors:
- Xinlu Ren
- Yi Dong
- Miao Duan
- Hui Zhang
- Peng Gao
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Affiliations: Department of Clinical Medicine, Queen Mary College of Nanchang University, Nanchang, Jiangxi 330031, P.R. China, Key Laboratory for Experimental Teratology of The Ministry of Education and Department of Pathology, School of Basic Medical Sciences, Shandong University, Jinan, Shandong 250012, P.R. China
Published online on: November 17, 2020 https://doi.org/10.3892/ol.2020.12307
Article Number: 46
Copyright: © Ren et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Hepatocarcinogenesis is a multistep process involving progression from cirrhosis, to low‑grade dysplastic nodule, to high‑grade dysplastic nodule (HGDN) and, eventually, to hepatocellular carcinoma (HCC). Early detection of HCC is challenging as the differential diagnosis between HGDN and early HCC (eHCC) is difficult. The aim of the present study was to identify a novel biomarker to specifically differentiate between HGDN and eHCC, which may facilitate early diagnosis of HCC. Immunohistochemistry was performed to determine the expression of heterogeneous nuclear ribonucleoprotein A3 (HNRNPA3) in cirrhosis, dysplastic nodules (DNs), well‑differentiated HCC and progressed HCC. The staining was evaluated by assigning a staining intensity score of 0‑3 and a percentage of positively stained cells score of 0‑4. Receiver operator characteristic (ROC) curve analysis was used to assess the ability of HNRNPA3 expression to differentiate between DNs and HCC. HNRNPA3 expression increased in a stepwise trend in non‑tumor hepatic tissue, DNs, eHCC and progressed HCC. ROC curves revealed that HNRNPA3 expression could be used to differentiate between HGDN and eHCC, particularly in combination with glypican 3 (GPC3), with a specificity of 100%. Moreover, HNRNPA3 expression was associated with HCC differentiation. In addition, high expression of HNRNPA3 was found to be associated with poor survival rates in patients with HCC. These findings demonstrated that HNRNPA3 combined with GPC3 is a helpful diagnostic biomarker in the differential diagnosis during the multistep process of hepatocarcinogenesis, particularly in the differential diagnosis between HGDN and eHCC. To the best of our knowledge, this is the first study to report the significance of HNRNPA3 in hepatocarcinogenesis and its potential role in carcinogenesis.

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