Chen Shang-Wei, Zhou Hua-Fu, Zhang Han-Jie, He Rong-Quan, Huang Zhi-Guang, Dang Yi-Wu, Yang Xia, Liu Jun, Fu Zong-Wang, Mo Jun-Xian, Tang Zhong-Qing, Li Chang-Bo, Li Rong, Yang Li-Hua, Ma Jie, Yang Lin-Jie, Chen Gang
Department of Cardio-Thoracic Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, China.
Department of Pathology, The First Affiliated Hospital of Guangxi Medical University, Nanning, China.
Front Genet. 2021 Jan 22;11:583085. doi: 10.3389/fgene.2020.583085. eCollection 2020.
Esophageal squamous cell carcinoma (ESCC) is the major histological type of esophageal cancers worldwide. Transcription factor was seen highly expressed in a variety of tumors and was related to the degree of tumor differentiation, invasion, and metastasis. However, the clinical significance of had yet to be verified, and the mechanism of abnormal expression in ESCC was not clear. In this study, the comprehensive analysis and evaluation of expression in ESCC were completed by synthesizing in-house immunohistochemistry (IHC), clinical sample tissue RNA-seq (in-house RNA-seq), public high-throughput data, and literature data. We also explored the possible signaling pathways and target genes of in ESCC by combining the target genes of (displayed by ChIP-seq), differentially expressed genes (DEGs) of ESCC, and -related genes, revealing the potential molecular mechanism of in ESCC. In the present study, protein and mRNA expression levels in ESCC tissues were all significantly higher than in non-cancerous tissues. The pool standard mean difference (SMD) of the overall expression was 1.17 (95% CI: 0.72-1.62, < 0.01), and the area under curve (AUC) of the summary receiver operating characteristic (SROC) was 0.86 (95% CI: 0.83-0.89). By combining the target genes displayed by ChIP-seq of , DEGs of ESCC, and -related genes, it was observed that may interact with these genes through chemokines and cytokine signaling pathways. By constructing a protein-protein interaction (PPI) network and combining ChIP-seq data, we obtained four potential target genes, , , , and . The gene expression of had a strong positive correlation with and , which suggested that might positively regulate the expression of these two genes. In summary, the high expression of may play an important role in the formation of ESCC. These roles may be completed by regulating the downstream target genes and .
食管鳞状细胞癌（ESCC）是全球范围内食管癌的主要组织学类型。转录因子在多种肿瘤中高表达，且与肿瘤分化程度、侵袭及转移相关。然而，其临床意义尚未得到验证，且ESCC中该转录因子异常表达的机制尚不清楚。在本研究中，通过综合内部免疫组织化学（IHC）、临床样本组织RNA测序（内部RNA测序）、公共高通量数据及文献数据，完成了对ESCC中该转录因子表达的综合分析与评估。我们还通过整合该转录因子的靶基因（由ChIP-seq显示）、ESCC的差异表达基因（DEGs）及与之相关的基因，探索了其在ESCC中可能的信号通路及靶基因，揭示了该转录因子在ESCC中的潜在分子机制。在本研究中，ESCC组织中该转录因子的蛋白和mRNA表达水平均显著高于非癌组织。该转录因子总体表达的合并标准均数差（SMD）为1.17（95%CI：0.72 - 1.62，P < 0.01），汇总受试者工作特征曲线（SROC）的曲线下面积（AUC）为0.86（95%CI：0.83 - 0.89）。通过整合该转录因子ChIP-seq显示的靶基因、ESCC的DEGs及与之相关的基因，发现该转录因子可能通过趋化因子和细胞因子信号通路与这些基因相互作用。通过构建蛋白质-蛋白质相互作用（PPI）网络并结合ChIP-seq数据，我们获得了4个该转录因子的潜在靶基因，即[具体基因1]、[具体基因2]、[具体基因3]和[具体基因4]。[具体基因1]的基因表达与[具体基因2]和[具体基因3]呈强正相关，这表明该转录因子可能正向调节这两个基因的表达。总之，该转录因子的高表达可能在ESCC的形成中起重要作用。这些作用可能通过该转录因子调节下游靶基因[具体基因2]和[具体基因3]来完成。
