Zhang Zhongbao, Meng Guangju, Wang Liang, Ma Yingying, Guan Zhongzheng
Department of General Surgery, The Third People's Hospital of Liaocheng, Liaocheng, Shandong 252000, P.R. China.
Department of Infectious Diseases, Tai'an Center Hospital, Tai'an, Shandong 271000, P.R. China.
Mol Med Rep. 2016 Jul;14(1):254-62. doi: 10.3892/mmr.2016.5261. Epub 2016 May 12.
The current study aimed to investigate the potential role of the FOXJ2 (forkhead box J2) protein in the pathology of hepatocellular carcinoma (HCC). Western blotting was performed to determine the expression levels of FOXJ2 in HCC tissues and HCC cells. Specimens from 110 patients with HCC undergoing hepatic resection were evaluated for FOXJ2 expression using an immunohistochemical assay. The correlation between FOXJ2 expression and clinicopathological factors of the patients was determined by statistical analysis to determine the prognostic merit of FOXJ2 expression in HCC. The detailed involvement of FOXJ2 in the regulation of HCC proliferation was further investigated using FOXJ2‑targeting small interfering RNA (siRNA). FOXJ2 protein was identified to be significantly downregulated in HCC tissues compared with adjacent normal liver tissues. Immunohistochemical analysis demonstrated that the expression of FOXJ2 was negatively correlated with Ki‑67 levels in HCC specimens (r=‑0.679, P<0.001). Furthermore, statistical analysis indicated FOXJ2 expression was significantly associated with histological differentiation (P=0.005), the size of largest tumor (P=0.002) and metastasis (P=0.036). Using Kaplan‑Meier analysis, it was demonstrated that high FOXJ2 expression levels predicted significantly improved patient survival rates compared with low FOXJ2 expression levels (P<0.001). In addition, it was observed that interference of FOXJ2 expression using siRNA oligos led to the promotion of proliferation of HepG2 cells. FOXJ2 was markedly downregulated in HCC tissues. The expression of FOXJ2 was correlated with tumor size, histological differentiation and metastasis. Low expression levels of FOXJ2 predicted poor prognosis for patients with HCC, suggesting that FOXJ2 may be a candidate prognostic marker of HCC. Depletion of FOXJ2 caused the promotion of HCC cell proliferation, implicating that FOXJ2 may serve an inhibitory role in the regulation of HCC cell proliferation.
本研究旨在探讨FOXJ2（叉头框J2）蛋白在肝细胞癌（HCC）病理过程中的潜在作用。采用蛋白质免疫印迹法检测HCC组织和HCC细胞中FOXJ2的表达水平。对110例行肝切除术的HCC患者的标本进行免疫组织化学检测，评估FOXJ2的表达情况。通过统计分析确定FOXJ2表达与患者临床病理因素之间的相关性，以确定FOXJ2表达在HCC中的预后价值。使用靶向FOXJ2的小干扰RNA（siRNA）进一步研究FOXJ2在HCC增殖调控中的具体作用机制。结果发现，与相邻正常肝组织相比，HCC组织中FOXJ2蛋白显著下调。免疫组织化学分析表明，HCC标本中FOXJ2的表达与Ki-67水平呈负相关（r = -0.679，P < 0.001）。此外，统计分析表明FOXJ2表达与组织学分化（P = 0.005）、最大肿瘤大小（P = 0.002）和转移（P = 0.036）显著相关。通过Kaplan-Meier分析表明，与低FOXJ2表达水平相比，高FOXJ2表达水平预示患者生存率显著提高（P < 0.001）。此外，观察到使用siRNA寡核苷酸干扰FOXJ2表达可导致HepG2细胞增殖增加。FOXJ2在HCC组织中明显下调。FOXJ2的表达与肿瘤大小、组织学分化和转移相关。FOXJ2低表达预示HCC患者预后不良，提示FOXJ2可能是HCC的一个候选预后标志物。FOXJ2的缺失导致HCC细胞增殖增加，这表明FOXJ2可能在HCC细胞增殖调控中起抑制作用。
