癌基因间脑/中脑同源框1(DMBX1)在多种人类癌症中广泛过表达。本研究旨在分析DMBX1在肝细胞癌(HCC)患者的非肿瘤组织和肿瘤组织中的表达及其临床意义。
使用免疫组织化学染色分析了DMBX1在HCC和邻近的非肿瘤组织中的表达。应用卡方检验来比较肿瘤和邻近正常组织之间的DMBX1表达。我们探讨了DMBX1表达与临床病理因素的相关性及其对HCC预后的影响。最后,我们通过敲低实验研究了DMBX1在肝癌中的作用,分析了细胞侵袭的变化,细胞增殖和上皮间质转化(EMT)生物标志物(E-cadherin,N-钙黏着蛋白,波形蛋白)。在HCC中与DMBX1共表达的mRNA,基于TCGA队列(n=366),是从cBioPortal数据库获得的。
DMBX1表达的平均得分在HCC和配对的邻近非肿瘤组织之间有显著差异(P<0.001),和DMBX1表达与乙型肝炎病毒(HBV)感染相关,肿瘤大小,转移,肿瘤淋巴结转移(TNM)分期(P<0.05)。多变量Cox回归分析确定了DMBX1表达与肿瘤转移的显着相关性,TNM阶段,和肿瘤包膜。此外,Kaplan-Meier生存分析显示,DMBX1过表达与HCC患者总生存期缩短之间存在相关性(P<0.05)。在HCC细胞系中,沉默DMBX1显著抑制迁移,增殖和EMT标记。选择与DMBX1mRNA共表达的阴性(R≤-0.25,n=1094)或阳性(R≥0.25,n=2906)的mRNA进行进一步的基因本体论富集分析。结果表明,DMBX1在肝癌中的预测功能支持体外实验结果。
我们的数据提供了DMBX1过表达与HCC转移和不良预后相关的证据。表明DMBX1是HCC的治疗靶点。
The oncogene diencephalon/mesencephalon homeobox 1 (
DMBX1) is widely overexpressed in a variety of human cancers. The present study aimed to analyze the expression and clinical importance of
DMBX1 in nonneoplastic tissues and tumor tissues from patients with hepatocellular carcinoma (HCC).
DMBX1 expression in HCC and adjacent nontumor tissues was analyzed using immunohistochemical staining. Chi-square tests were applied to compare
DMBX1 expression between the tumors and the adjacent normal tissues. We explored the correlation of DMBX1 expression with clinicopathological factors and its effect on the prognosis of HCC. Finally, we investigated the role of DMBX1 in HCC via knockdown experiments, which analyzed changes in cell invasion, cell proliferation and epithelial-mesenchymal transition (EMT) biomarkers (E-cadherin, N-cadherin, vimentin). The mRNAs that were coexpressed with DMBX1 in HCC, based on the TCGA cohort (n = 366), were obtained from the cBioPortal database.
The average score for DMBX1 expression was significantly different (P < 0.001) between HCC and paired adjacent nontumor tissues, and DMBX1 expression correlated with hepatitis B virus (HBV) infection, tumor size, metastasis, and tumor node metastasis (TNM) stage (P < 0.05). A multivariate Cox regression analysis identified significant correlations of DMBX1 expression with tumor metastasis, TNM stage, and tumor capsule. Moreover, Kaplan-Meier survival analysis revealed an association between DMBX1 overexpression and shorter overall survival of patients with HCC (P < 0.05). In HCC cell lines, silencing
DMBX1 markedly inhibited migration, proliferation and EMT markers. The mRNAs that were negatively (R ≤ -0.25, n = 1094) or positively (R ≥ 0.25, n = 2906) coexpressed with DMBX1 mRNA were selected for further Gene Ontology enrichment analysis, and the results revealed that the predicted functions of DMBX1 in HCC support the in vitro experimental results.
Our data provide evidence that DMBX1 overexpression is associated with HCC metastasis and poor prognosis, suggesting that
DMBX1 represents a therapeutic target in HCC.