Nambara Sho, Masuda Takaaki, Tobo Taro, Kidogami Shinya, Komatsu Hisateru, Sugimachi Keishi, Saeki Hiroshi, Oki Eiji, Maehara Yoshihiko, Mimori Koshi
Department of Surgery, Kyushu University Beppu Hospital, Beppu, Oita 874-0838, Japan.
Department of Pathology, Kyushu University Beppu Hospital, Beppu, Oita 874-0838, Japan.
Oncol Lett. 2017 Aug;14(2):1795-1801. doi: 10.3892/ol.2017.6341. Epub 2017 Jun 8.
The present authors previously identified a novel candidate tumor suppressor gene, zinc finger protein 750 (), in esophageal squamous cell carcinoma (ESCC) (1). The present study aimed to clarify the clinical significance of expression in ESCC. The association between DNA mutation status and the mRNA expression was examined by whole exome sequence analysis and quantitative reverse transcription polymerase chain reaction (RT-qPCR). The expression of in 76 patients with ESCC (Kyushu University Beppu Hospital) was measured using immunohistochemistry and RT-qPCR. Using this dataset, the association between mRNA expression and clinicopathological factors was examined. Additionally, survival analysis was performed using datasets from the Kyushu University Beppu Hospital and The Cancer Genome Atlas (TCGA). The biological effects of expression were explored using gene set enrichment analysis (GSEA) and were validated using datasets from the Cancer Cell Line Encyclopedia (CCLE) and the Kyushu University Beppu Hospital. expression analyses demonstrated that mRNA expression was lower in patients with the DNA mutations compared with those without the mutations (P<0.05), and expression was downregulated in tumor tissues compared with normal tissues (P<0.00005). In the clinicopathological analysis, the low expression group exhibited a higher incidence of undifferentiated histology (P<0.05) compared with the high expression group. The low expression group exhibited a poorer prognosis in the Kyushu and TCGA datasets (P<0.0005 and P<0.05, respectively). GSEA indicated that expression was significantly correlated with epithelial differentiation in ESCC. This was confirmed using the datasets from CCLE and the Kyushu University Beppu Hospital by analyzing the levels of small proline rich protein 1A mRNA, an epithelial differentiation-associated gene. In conclusion, the results of the present study suggested that serves a role as a tumor suppressor; potentially via regulating epithelial differentiation and that it may be a promising biomarker of poor outcomes in ESCC.
本研究作者之前在食管鳞状细胞癌(ESCC)中鉴定出一个新的候选肿瘤抑制基因——锌指蛋白750(ZNF750)(1)。本研究旨在阐明ZNF750在ESCC中的表达的临床意义。通过全外显子组序列分析和定量逆转录聚合酶链反应(RT-qPCR)检测ZNF750 DNA突变状态与mRNA表达之间的关联。使用免疫组织化学和RT-qPCR检测76例ESCC患者(九州大学别府医院)中ZNF750的表达。利用该数据集,检测ZNF750 mRNA表达与临床病理因素之间的关联。此外,使用来自九州大学别府医院和癌症基因组图谱(TCGA)的数据集进行生存分析。利用基因集富集分析(GSEA)探索ZNF750表达的生物学效应,并使用来自癌症细胞系百科全书(CCLE)和九州大学别府医院的数据集进行验证。ZNF750表达分析表明,与无DNA突变的患者相比,有DNA突变的患者中ZNF750 mRNA表达较低(P<0.05),与正常组织相比,肿瘤组织中ZNF750表达下调(P<0.00005)。在临床病理分析中,与高表达组相比,低ZNF750表达组未分化组织学的发生率更高(P<0.05)。在九州和TCGA数据集中,低ZNF750表达组的预后较差(分别为P<0.0005和P<0.05)。GSEA表明,ZNF750表达与ESCC中的上皮分化显著相关。通过分析上皮分化相关基因富含脯氨酸的小蛋白1A mRNA的水平,使用来自CCLE和九州大学别府医院的数据集证实了这一点。总之,本研究结果表明ZNF750作为一种肿瘤抑制因子发挥作用;可能是通过调节上皮分化,并且它可能是ESCC预后不良的一个有前景的生物标志物。