High ADAM8 expression is associated with poor prognosis in patients with hepatocellular carcinoma
Authors: Kai Zhang
Chao Jiang
Yong-Fei Tan
Miao Zhang
Tian-Zhou Zha
Yun Zhang
Journal: Pathology & Oncology Research (2013)
Discipline: CLINICAL MEDICINE
Keywords: ADAM8 expression; hepatocellular carcinoma; clinicopathologic features; survival; biological processes
Affiliations: Department of General Surgery, Yixing People's Hospital, No. 75, Tongzhen Guan Rd., Yixing 214200, China.

Abstract:  In this study,we investigated the ADAM8 expression in hepatocellular carcinoma (HCC) and its correlation with clinicopathologic features,including the survival of patients with HCC. Furthermore,we examined the biological processes regulated by ADAM8 during the development of using HepG2 cell line as a model system. We used immunohistochemistry to compare ADAM8 protein expression in HCC and normal liver tissues and further analyze the ADAM8 protein expression in clinicopathologically characterized 105 HCC cases.We stably knocked down the endogenous expression level of ADAM8 in HepG2 cells with specific shRNA-expressing lentiviral vector. Following the successful establishment of stable cells,we examined in vitro cell growth by MTT assay,anchorage-independent growth by soft-agar colony formation assay and cell migration/invasion by transwell and boyden chamber assay. And in addition,we also investigated the in vivo tumor growth by xenograft transplantation of HepG2 cells into nude mice. Protein expression level of ADAM8 was markedly higher in HCC tissues than that in the normal liver tissues (P = 0.0058).In addition,high expression of ADAM8 protein was positively correlated with serum AFP elevation,tumor size,histological differentiation,tumor recurrence,tumor metastasis,and tumor stage. Patients with higher ADAM8 expression showed a significantly shorter overall survival time than patients with low ADAM8 expression. Multivariate analysis suggested that ADAM8 expression might be an independent prognostic indicator (p = 0.016) for the survival of patients with HCC. ADAM8-specific shRNA (shADAM8) successfully knocked down its endogenous expression in HepG2 cells. Compared to the parental and control shRNA-transfected (shCtrl) HepG2 cells,the shADAM8 cells exhibited significantly reduced in vitro cell growth,anchorage-independent growth,cell migration and invasion (p &lt; 0.05).In vivo,the xenograft transplants from shADAM8 cells gave rise to much smaller tumors as compared to those from shCtrl cells. High ADAM8 expression is associated with poor overall survival in patients with HCC. Down-regulation of ADAM8 inhibits the growth,anchorage-independent growth,migration and invasion of HepG2 cells. ADAM8 may be a potential target of antiangiogenic therapy for HCC. 

Retracted: No

PubPeer comments:
 Posting a concern by another reader. In Figure 2, The GAPDH panel shown in Figure 1A appears to look similar to the GAPDH panel belonging to the MEK1 2 expression. Note the different incubation times. ![file] , 
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 retraction on Aug 21, 2020 : http: m.jbc.org content 295 34 12329  This article has been withdrawn by Bo-Jian Zheng, Dong-Yan Jin, Xuetao Cao, and Liwei Lu. Queenie Lai Kwan Lam could not be reached. The JAK2 immunoblot in Fig. 2A was duplicated as STAT-1u03b1 in Fig. 2B. The GAPDH immunoblot in Fig. 2A was duplicated in Fig. 2B in the MEK1 2 panel. In Fig. 2B, the GAPDH immunoblots in the NF-u03baB and STAT-1u03b1 panels are the same. In Fig. 2C, the Akt, mTOR, STAT-1u03b1, and MEK1 2 immunoblots are the same. The withdrawing authors apologize for not detecting the duplicated panels at the submission and publication of this article. When this issue was brought to their attention, the original data obtained 15 years ago could not be located. However, the withdrawing authors state that they have repeated the experiments shown in Fig. 2 (B and C) and that they were able to confirm the results shown in these two panels. ,