CRBP-1 over-expression is associated with poor prognosis in tongue squamous cell carcinoma.
CRBP-1 over-expression is associated with poor prognosis in tongue squamous cell carcinoma.
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DOI：
10.1186/s12885-018-4249-1
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发表时间：
2018-05-02
期刊：
影响因子：
3.8
通讯作者：
Li H
中科院分区：
文献类型：
--
作者：
Chen Y;Tian T;Mao MJ;Deng WY;Li H
舌鳞状细胞癌是口腔鳞状细胞癌中最常见的恶性肿瘤之一。细胞视黄醇结合蛋白-1(CRBP-1)作为载体蛋白将视黄醇从肝脏储存部位转运到外周组织。CRBP-1的表达上调与前列腺癌、乳腺癌和卵巢癌等肿瘤类型有关，但其在TSCC中的作用尚不清楚。本研究基于肿瘤数据库中的多种肿瘤微阵列数据进行综合生物信息学分析，以观察CRBP-1在舌鳞癌和癌旁非肿瘤组织中的差异表达。应用实时定量聚合酶链式反应(qRT-PCR)、免疫印迹(WB)和免疫组织化学(IHC)方法检测101例TSCC组织和48对新鲜冰冻组织中CRBP-1的表达。采用Kaplan-Meier曲线、单因素和多因素Cox回归分析CRBP-1的表达与患者预后的关系。采用免疫印迹、四甲基偶氮唑盐比色法、跨膜迁移和侵袭实验观察CRBP-1对TSCC细胞增殖和侵袭能力的影响。与配对的癌旁非肿瘤组织相比，喉癌组织中CRBP-1的表达显著上调，其表达与肿瘤分化程度(P = 0.003)、N分期(P = 0.048)、临床分期(P = 0.048)和死亡(P = 0.001)有关。Kaplan-Meier曲线显示，CRBP-1高表达的TSCC患者的总生存率低于CRBP-1低表达的患者。单因素和多因素分析显示，CRBP-1是一个独立的预后因素(P <； 0.05)。此外，我们还下调了CRBP-1的表达，并通过四甲基偶氮唑盐比色法和Transwell法观察到体外培养的TSCC细胞的增殖和侵袭能力明显受阻。CRBP-1的表达上调与TSCC的预后不良有关，因此CRBP-1的表达可能作为一种新的预后指标，抑制CRBP-1的表达可能为TSCC提供新的治疗途径。
Tongue squamous cell carcinoma (TSCC) is one of the most common malignancies of oral squamous cell carcinomas. Cellular retinol binding protein-1 (CRBP-1) as a carrier protein transports retinol from the liver storage site to peripheral tissue. Up-regulated expression of CRBP-1 is associated with some tumor types such as prostate cancer, breast cancer and ovarian cancer as reported, but its role in TSCC remains uncertain. In this study, an integrated bioinformatics analysis based on the multiple cancer microarray data sets available from Oncomine database was conducted to view the differential expression of CRBP-1 between TSCC and the adjacent non-tumorous tissues. Quantitative real-time polymerase chain reaction (qRT-PCR), western blotting (WB) and immunohistochemical (IHC) assays were performed to investigate CRBP-1 expression in 101 paraffin-embeded TSCC tissues and 48 pairs of freshly frozen tissues. Kaplan-Meier curve and univariate and multivariate Cox-regression analysis were used to estimate the association between CRBP-1 expression and patients’ prognosis. Then western blotting, MTT, transwell migration and invasion assays were performed in TSCC cell lines to investigate the effects of CRBP-1 on cellular proliferation and invasion. Compared with the matched adjacent non-tumorous tissues, the expression of CRBP-1 was significantly up-regulated in TSCC tissues, which correlated with the differentiation state (P = 0.003), N classification (P = 0.048), the clinical stage (P = 0.048) and death (P = 0.001). The Kaplan-Meier curve showed that TSCC patients with higher CRBP-1 expression levels had lower overall survival rates than those with lower CRBP-1 expression levels. A univariate and multivariate analysis demonstrated that CRBP-1 was an independent prognostic factor (P < 0.05). Furthermore, we knocked down CRBP-1 expression and observed that TSCC cell proliferation and invasion in vitro were significantly blocked, as determined by MTT and transwell assays. Up-regulated expression of CRBP-1 is associated with poor prognosis in TSCC, so it might potentially serve as an additional prognostic marker, and the inhibition of CRBP-1 might provide new therapeutic approaches for TSCC.
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