Zheng Liuhai, Li Linzhi, Xie Jun, Jin Hai, Zhu Naishuo
Laboratory of Molecular Immunology, State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, China.
Department of Thoracic Surgery, Changhai Hospital, Second Military Medical University, Shanghai, China.
J Cancer. 2021 Jan 1;12(3):899-911. doi: 10.7150/jca.50443. eCollection 2021.
Esophageal squamous cell carcinoma (ESCC) is one of the most common cancers worldwide. ESCC has a generally poor prognosis and there is a lack of available biomarkers for diagnosis and prognosis. The aim of the study was to identify novel biomarkers for ESCC. We screened the overlapping differentially expressed genes (DEGs) acquired from six Gene Expression Omnibus (GEO) ESCC datasets and The Cancer Genome Atlas (TCGA) ESCC datasets. Subsequently, protein-protein interaction network analysis was performed to identify the key hub genes. Then, Kaplan Meier survival and receiver operating curve (ROC) analysis were utilized to clarify the diagnostic and prognostic role of these hub genes. The UALCAN database, single cell RNA sequencing (scRNA-seq) and real-time quantitative PCR (qPCR) were performed to confirm the expression levels of identified hub genes. Finally, immune infiltration analysis was conducted to investigate the role of these genes in the pathogenesis of ESCC. The results showed that PBK, KIF2C, NUF2, KIF20A, RAD51AP1, and DEPDC1 effectively distinguish ESCC tissues from normal samples, and all of them were significantly correlated with overall survival. The results of scRNA-seq and qPCR indicated that the expression levels of hub genes in ESCC were significantly higher than in normal cells or tissues. Further immune infiltration analysis showed that infiltration of dendritic cells was significantly negatively correlated with PBK, KIF2C, NUF2, RAD51AP1, and DEPDC1 expression levels. In conclusion, our results suggest that PBK, KIF2C, NUF2, KIF20A, RAD51AP1 and DEPDC1 are all potential biomarkers for ESCC diagnosis and prognosis may also be potential therapeutic targets for ESCC.
食管鳞状细胞癌（ESCC）是全球最常见的癌症之一。ESCC的预后通常较差，并且缺乏用于诊断和预后的可用生物标志物。本研究的目的是鉴定ESCC的新型生物标志物。我们筛选了从六个基因表达综合数据库（GEO）的ESCC数据集和癌症基因组图谱（TCGA）的ESCC数据集中获得的重叠差异表达基因（DEG）。随后，进行蛋白质-蛋白质相互作用网络分析以鉴定关键的枢纽基因。然后，利用Kaplan Meier生存分析和受试者工作特征曲线（ROC）分析来阐明这些枢纽基因的诊断和预后作用。使用UALCAN数据库、单细胞RNA测序（scRNA-seq）和实时定量PCR（qPCR）来确认所鉴定枢纽基因的表达水平。最后，进行免疫浸润分析以研究这些基因在ESCC发病机制中的作用。结果表明，PBK、KIF2C、NUF2、KIF20A、RAD51AP1和DEPDC1能够有效区分ESCC组织与正常样本，并且它们均与总生存期显著相关。scRNA-seq和qPCR的结果表明，ESCC中枢纽基因的表达水平显著高于正常细胞或组织。进一步的免疫浸润分析表明，树突状细胞的浸润与PBK、KIF2C、NUF2、RAD51AP1和DEPDC1的表达水平显著负相关。总之，我们的结果表明，PBK、KIF2C、NUF2、KIF20A、RAD51AP1和DEPDC1都是ESCC诊断和预后的潜在生物标志物，也可能是ESCC的潜在治疗靶点。
