Department of Thoracic Surgery, Jining No. 1 People's Hospital, Jining, Shandong, China.
Eur Rev Med Pharmacol Sci. 2018 Jan;22(2):422-429. doi: 10.26355/eurrev_201801_14191.
The purpose of this study was to explore the clinical significance and biological function of long noncoding RNA CASC9 (CASC9) in esophageal squamous cell carcinoma (ESCC).
Quantitative Real-time PCR (qRT-PCR) was used to determine the expression of CASC9 in ESCC tissues and cell lines. Receiver operating characteristic curves were used to evaluate the sensitivity and specificity of CASC9. The correlation between the CASC9 levels and the clinicopathological factors of the patients was also analyzed. Then, the survival was assessed by the Kaplan-Meier method and proportional hazards model. The effects of CASC9 on ESCC cells were evaluated by Cell Counting Kit-8 (CCK-8), migration and invasion. Finally, several EMT markers expression was detected by Western blot.
We found that CASC9 was significantly upregulated in ESCC cell lines and clinical tissues. The CASC9 levels discriminated ESCC tissues from normal tissues with an area under the ROC curve (AUC) of 0.813. In addition, there is statistical significance between CASC9 expression level and tumor stage, lymph nodes metastasis, and clinical stage. Kaplan-Meier analysis indicated that high CASC9 expression had a significant impact on overall survival (p = 0.014) and disease-free survival (p = 0.0025). Moreover, CASC9 expression was an independent prognostic marker of overall survival and disease-free survival in a multivariate analysis. In vitro assay indicated that inhibition of CASC9 could suppress proliferation, migration, and invasion in ESCC. Further mechanistic studies found that aberrant CASC9 expression could modulate the expression levels of markers of EMT.
Our data highlight the pivotal role of CASC9 as a novel diagnostic, prognostic biomarker and a potential therapeutic target of ESCC.
本研究旨在探讨长链非编码 RNA CASC9(CASC9)在食管鳞状细胞癌(ESCC)中的临床意义和生物学功能。
采用实时定量 PCR(qRT-PCR)检测 ESCC 组织和细胞系中 CASC9 的表达。绘制受试者工作特征曲线评估 CASC9 的灵敏度和特异性。分析 CASC9 水平与患者临床病理因素的相关性。然后,采用 Kaplan-Meier 方法和比例风险模型评估生存情况。通过细胞计数试剂盒-8(CCK-8)、迁移和侵袭实验评估 CASC9 对 ESCC 细胞的影响。最后,通过 Western blot 检测几种 EMT 标志物的表达。
我们发现 CASC9 在 ESCC 细胞系和临床组织中显著上调。CASC9 水平可将 ESCC 组织与正常组织区分开来,ROC 曲线下面积(AUC)为 0.813。此外,CASC9 表达水平与肿瘤分期、淋巴结转移和临床分期之间存在统计学意义。Kaplan-Meier 分析表明,高 CASC9 表达对总生存(p = 0.014)和无病生存(p = 0.0025)有显著影响。此外,多因素分析表明 CASC9 表达是总生存和无病生存的独立预后标志物。体外实验表明,抑制 CASC9 可抑制 ESCC 的增殖、迁移和侵袭。进一步的机制研究发现,异常的 CASC9 表达可调节 EMT 标志物的表达水平。
我们的数据强调了 CASC9 作为 ESCC 的新型诊断、预后生物标志物和潜在治疗靶点的重要作用。