Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, 651 Dong Feng Road East, Guangzhou, Guangdong, 510060, China.
Department of head and neck surgery, Sun Yat-sen University Cancer Center, 651 Dong Feng Road East, Guangzhou, Guangdong, 510060, China.
BMC Cancer. 2018 May 2;18(1):514. doi: 10.1186/s12885-018-4249-1.
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.
舌鳞状细胞癌（TSCC）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）作为一种载体蛋白，将视黄醇从肝脏储存部位转运到外周组织。据报道，上调的 CRBP-1 表达与一些肿瘤类型相关，如前列腺癌、乳腺癌和卵巢癌，但它在 TSCC 中的作用仍不确定。
本研究基于 Oncomine 数据库中可用的多个癌症微阵列数据集，进行了综合的生物信息学分析，以观察 CRBP-1 在 TSCC 与相邻非肿瘤组织之间的差异表达。采用定量实时聚合酶链反应（qRT-PCR）、Western blot（WB）和免疫组织化学（IHC）检测 101 例石蜡包埋的 TSCC 组织和 48 对新鲜冷冻组织中 CRBP-1 的表达。Kaplan-Meier 曲线和单变量及多变量 Cox 回归分析用于估计 CRBP-1 表达与患者预后之间的关系。然后在 TSCC 细胞系中进行 Western blot、MTT、transwell 迁移和侵袭实验，以研究 CRBP-1 对细胞增殖和侵袭的影响。
与匹配的相邻非肿瘤组织相比，CRBP-1 在 TSCC 组织中的表达明显上调，且与分化状态（P=0.003）、N 分类（P=0.048）、临床分期（P=0.048）和死亡（P=0.001）相关。Kaplan-Meier 曲线显示，CRBP-1 表达水平较高的 TSCC 患者总生存率低于 CRBP-1 表达水平较低的患者。单变量和多变量分析表明，CRBP-1 是一个独立的预后因素（P<0.05）。此外，我们敲低了 CRBP-1 的表达，发现 MTT 和 transwell 实验表明，TSCC 细胞的体外增殖和侵袭明显受到抑制。
CRBP-1 的上调表达与 TSCC 的不良预后相关，因此它可能作为一个额外的预后标志物，抑制 CRBP-1 可能为 TSCC 提供新的治疗方法。
