Open Access Research article

A novel panel of biomarkers in distinction of small well-differentiated HCC from dysplastic nodules and outcome values

Guang-Zhi Jin1, Hui Dong1, Wen-Long Yu2, Yan Li3, Xin-Yuan Lu1, Hua Yu1, Zhi-Hong Xian1, Wei Dong1, Yin-Kun Liu3*, Wen-Ming Cong1* and Meng-Chao Wu4

Author Affiliations

1 Department of Pathology, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, 200438, China

2 Department II of billiary tract Surgery, Eastern Hepatobiliary Hospital, Second Military Medical University, Shanghai, 200438, China

3 Liver Cancer Institute, Zhong Shan Hospital & Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, China

4 Department of Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, 200438, China

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BMC Cancer 2013, 13:161  doi:10.1186/1471-2407-13-161

Published: 27 March 2013



Differential diagnosis of high-grade dysplastic nodules (HGDN) and well-differentiated hepatocellular carcinoma (WDHCC) represents a challenge to experienced hepatic clinicians, radiologists and hepatopathologists.


The expression profiles of aminoacylase-1 (ACY1), sequestosome-1 (SQSTM1) and glypican-3 (GPC3) in low-grade dysplastic nodules (LGDN), HGDN and WDHCC were assessed by immunohistochemistry. The differential diagnostic performances of these three markers alone and in combination for HGDN and WDHCC were investigated by logistic regression models (HGDN = 21; WDHCC = 32) and validated in an independent test set (HGDN, n = 21; WDHCC n = 24). Postoperative overall survival and time to recurrence were evaluated by univariate and multivariate analyses in an independent set of 500 patients.


ACY1, SQSTM1 and GPC3 were differentially expressed in each group. For the differential diagnosis of WDHCC from HGDN, the sensitivity and specificity of the combination of ACY1 + SQSTM1 + GPC3 for detecting WDHCC were 93.8% and 95.2% respectively in the training set, which were higher than any of the three two-marker combinations. The validities of the four diagnostic models were further confirmed in an independent test set, and corresponding good sensitivity and specificity were observed. Interestingly, GPC3 expression in HCC tissues combined with serum α-fetoprotein (AFP) was found to be an independent predictor for overall survival and time to recurrence.


ACY1 + SQSTM1 + GPC3 combination represents a potentially valuable biomarker for distinguishing between WDHCC and HGDN using immunohistochemistry. Meanwhile, low GPC3 staining combined with positive serum AFP may play a practical role in predicting poor postoperative outcome and high tumor recurrence risk.

High grade dysplastic nodules; Well-differentiated hepatocellular carcinoma; Aminoacylase-1; Sequestosome-1; Glypican-3