Department of Intensive Care Unit, The Fourth Hospital of Hebei Medical University, Shijiazhuang, 050011 Hebei, China.
Department of Emergency (Xiangjiang Hospital), The Third Hospital of Hebei Medical University, Shijiazhuang, 050051 Hebei, China.
Biomed Res Int. 2022 Jul 27;2022:5328192. doi: 10.1155/2022/5328192. eCollection 2022.
OBJECTIVE: Endothelial cell-specific molecule 1 (ESM1) has been implicated as an oncogene in several types of cancer. However, the potential role of ESM1 in esophageal carcinogenesis (ESCA)/esophageal squamous cell carcinoma (ESCC) is still unclear. METHODS: The expression, function, and survival data of ESM1 were observed using a bioinformatics approach. Subsequently, the expression level of ESM1 in surgical esophageal tumors and adjacent normal tissues was detected by qRT-PCR and immunofluorescence. We further revealed protein expression by immunohistochemistry (IHC), which is related to the prognosis of patients with ESCC using survival analysis. In vitro, knockdown of ESM1 in KYSE150 and KYSE510 cell lines, colony formation assays, wound healing assays, and Transwell assays were performed. RESULTS: ESM1 is significantly elevated in 12 of 20 types of human cancer. ESM1 is highly expressed in tumor tissue compared with adjacent normal tissue and was identified as a hub gene in ESCA. Clinical outcome endpoints of overall survival (OS), progression-free interval (PFI), and disease-specific survival (DSS) curves showed that patients whose ESM1 expression was high had a lower clinical survival rate. The ESM1 high-expression group has a certain correlation with clinical stage and grade. The IHC of ESM1 further demonstrated that the higher the expression was, the worse the N classification and pTNM stage in patients with ESCC, which had a distinctly poorer overall 5-year survival rate. Univariate analysis showed that age, N classification, pTNM stage, and ESM1 expression were all prognostic factors, although multivariate Cox regression analysis showed that only pTNM stage was an independent prognostic factor. In vitro, silencing ESM1 suppressed the proliferation, migration, and invasion of KYSE150 and KYSE510 cells. CONCLUSIONS: ESM1 is a hub gene in the initiation and progression of ESCA/ESCC that promotes the proliferation, migration, and invasion of esophageal cancer cells and may be a promising therapeutic target and prognostic indicator.
目的:内皮细胞特异性分子 1(ESM1)已被认为是多种癌症的癌基因。然而,ESM1 在食管癌变(ESCA)/食管鳞状细胞癌(ESCC)中的潜在作用尚不清楚。
方法:使用生物信息学方法观察 ESM1 的表达、功能和生存数据。随后,通过 qRT-PCR 和免疫荧光检测手术食管肿瘤和相邻正常组织中 ESM1 的表达水平。我们进一步通过免疫组化(IHC)揭示了与 ESCC 患者预后相关的蛋白质表达,通过生存分析。在体外,在 KYSE150 和 KYSE510 细胞系中敲低 ESM1,进行集落形成试验、划痕愈合试验和 Transwell 试验。
结果:ESM1 在 20 种人类癌症中的 12 种中显著升高。ESM1 在肿瘤组织中的表达明显高于相邻的正常组织,并且被鉴定为 ESCA 的枢纽基因。总生存(OS)、无进展间隔(PFI)和疾病特异性生存(DSS)曲线的临床结局终点表明,ESM1 表达高的患者临床生存率较低。ESM1 高表达组与临床分期和分级有一定的相关性。ESM1 的 IHC 进一步表明,ESCC 患者的 N 分类和 pTNM 分期越高,表达越高,总 5 年生存率越差。单因素分析表明,年龄、N 分类、pTNM 分期和 ESM1 表达均为预后因素,尽管多因素 Cox 回归分析表明只有 pTNM 分期是独立的预后因素。在体外,沉默 ESM1 抑制了 KYSE150 和 KYSE510 细胞的增殖、迁移和侵袭。
结论:ESM1 是 ESCA/ESCC 发生和发展的枢纽基因,促进食管癌细胞的增殖、迁移和侵袭,可能是一种有前途的治疗靶点和预后指标。
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