Song Yexun, Wang Xianyao, Wang Fengjun, Peng Xiaowei, Li Peiyu, Liu Shaojun, Zhang Decai
Department of Otolaryngology-Head Neck Surgery, The Third Xiangya Hospital of Central South University, Changsha, 410013, Hunan, China.
Department of Otolaryngology-Head Neck Surgery, The Xiangya Hospital of Central South University, Changsha, 410008, Hunan, China.
Cancer Cell Int. 2021 Feb 18;21(1):123. doi: 10.1186/s12935-021-01814-1.
Esophageal squamous cell carcinoma (ESCC) has become one of the most serious diseases affecting populations worldwide and is the primary subtype of esophageal cancer (EC). However, the molecular mechanisms governing the development of ESCC have not been fully elucidated.
The robust rank aggregation method was performed to identify the differentially expressed genes (DEGs) in six datasets (GSE17351, GSE20347, GSE23400, GSE26886, GSE38129 and GSE77861) from the Gene Expression Omnibus (GEO). The Search Tool for the Retrieval of Interacting Genes (STRING) database was utilized to extract four hub genes from the protein-protein interaction (PPI) network. Module analysis and disease free survival analysis of the four hub genes were performed by Cytoscape and GEPIA. The expression of hub genes was analyzed by GEPIA and the Oncomine database and verified by real-time quantitative PCR (qRT-PCR).
In total, 720 DEGs were identified in the present study; these genes consisted of 302 upregulated genes and 418 downregulated genes that were significantly enriched in the cellular component of the extracellular matrix part followed by the biological process of the cell cycle phase and nuclear division. The primary enriched pathways were hsa04110:Cell cycle and hsa03030:DNA replication. Four hub genes were screened out, namely, SPP1, MMP12, COL10A1 and COL5A2. These hub genes all exhibited notably increased expression in ESCC samples compared with normal samples, and ESCC patients with upregulation of all four hub genes exhibited worse disease free survival.
SPP1, MMP12, COL10A1 and COL5A2 may participate in the tumorigenesis of ESCC and demonstrate the potential to serve as molecular biomarkers in the early diagnosis of ESCC. This study may help to elucidate the molecular mechanisms governing ESCC and facilitate the selection of targets for early treatment and diagnosis.
食管鳞状细胞癌（ESCC）已成为影响全球人群的最严重疾病之一，是食管癌（EC）的主要亚型。然而，ESCC发生发展的分子机制尚未完全阐明。
采用稳健秩聚合方法，从基因表达综合数据库（GEO）的六个数据集（GSE17351、GSE20347、GSE23400、GSE26886、GSE38129和GSE77861）中鉴定差异表达基因（DEGs）。利用搜索互作基因的工具（STRING）数据库从蛋白质-蛋白质相互作用（PPI）网络中提取四个核心基因。通过Cytoscape和GEPIA对这四个核心基因进行模块分析和无病生存分析。通过GEPIA和Oncomine数据库分析核心基因的表达，并通过实时定量PCR（qRT-PCR）进行验证。
本研究共鉴定出720个DEGs；这些基因包括302个上调基因和418个下调基因，它们在细胞外基质部分的细胞成分中显著富集，其次是细胞周期阶段和核分裂的生物学过程。主要富集的通路为hsa04110：细胞周期和hsa03030：DNA复制。筛选出四个核心基因，即SPP1、MMP12、COL10A1和COL5A2。与正常样本相比，这些核心基因在ESCC样本中的表达均显著增加，且四个核心基因均上调的ESCC患者无病生存期较差。
SPP1、MMP12、COL10A1和COL5A2可能参与ESCC的肿瘤发生，并具有作为ESCC早期诊断分子生物标志物的潜力。本研究可能有助于阐明ESCC的分子机制，并促进早期治疗和诊断靶点的选择。
