Radiation Oncology Department of Gastrointestinal Cancer and Lymphoma, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, China.
Biomed Res Int. 2020 Aug 22;2020:6387519. doi: 10.1155/2020/6387519. eCollection 2020.
Esophageal squamous cell carcinoma (ESCC) is a leading malignancy with both high incidence and mortality worldwide. However, the molecular mechanisms of the poor prognosis in ESCC are still unclear.
We conducted differential expression analysis between ESCC and normal tissues and between ESCC samples with and without CNAs in a given gene. Overrepresentation enrichment and gene set enrichment analyses were used to identify the oncogenic pathways and abnormal transcription factors (TFs). The survival analysis was employed to identify the genes associated with overall survival.
In this study, we aimed to identify and interpret the driver genes triggered by the copy number alterations (CNAs), including CCND1, TEAD4, EIF4EBP1, EGFR, FGFR3, and FZD6. Furthermore, we identified oncogenic pathways, including RTK-RAS, WNT, PI3K, Hippo, and cell cycle, and key TFs including TEAD4, a transcription factor in the Hippo signaling pathway, and LEF1 in the WNT signaling pathway. Furthermore, we observed that upregulations of FGFR3 and EIF4EBP1 were significantly associated with shorter overall survival in ESCC.
In conclusion, the driver genes triggered by CNAs not only exhibited critical functionality but also were clinically relevant in ESCC, which greatly improved our understanding of the molecular mechanisms in ESCC.
食管鳞状细胞癌（ESCC）是一种发病率和死亡率都很高的主要恶性肿瘤。然而，ESCC 预后不良的分子机制仍不清楚。
我们对 ESCC 和正常组织之间以及在给定基因中存在和不存在拷贝数改变（CNA）的 ESCC 样本之间进行了差异表达分析。过表达富集和基因集富集分析用于鉴定致癌途径和异常转录因子（TFs）。生存分析用于鉴定与总生存相关的基因。
在这项研究中，我们旨在识别和解释由拷贝数改变（CNAs）触发的驱动基因，包括 CCND1、TEAD4、EIF4EBP1、EGFR、FGFR3 和 FZD6。此外，我们还鉴定了致癌途径，包括 RTK-RAS、WNT、PI3K、Hippo 和细胞周期，以及关键的 TF，包括 Hippo 信号通路中的 TEAD4 和 WNT 信号通路中的 LEF1。此外，我们观察到 FGFR3 和 EIF4EBP1 的上调与 ESCC 患者的总生存期较短显著相关。
总之，由 CNA 触发的驱动基因不仅具有关键的功能，而且在 ESCC 中具有临床相关性，这极大地提高了我们对 ESCC 分子机制的理解。
