ESM1 Is a Promising Therapeutic Target and Prognostic Indicator for Esophageal Carcinogenesis/Esophageal Squamous Cell Carcinoma

Abstract

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.

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“…Endothelial cell-specific molecule 1 (ESM1), a secreted proteoglycan, is overexpressed in several malignant tumors and highly associated with tumor metastasis. Thus, ESM1 is regarded as a promising therapeutic target for several tumors. , Given that ESM1 was the most significant differential gene among all 1560 DEGs, we further investigated the expression level of ESM1 in six groups via a Western blot assay. Notably, the expression of ESM1 was significantly decreased after treatment with T-HCN@CuMS+L, which was consistent with the results of migration and invasion assays (Figure E).…”

Roles of endothelial cell specific molecule‑1 in tumor angiogenesis (Review)

“…For example, clinical investigations have observed increased ESM1 levels in secretions or serum from patients with nasopharyngeal, endometrial and ovarian carcinoma ( 18 , 19 ). In addition, elevated ESM1 expression has been observed in cancer cells, including cervical cancer, squamous cell cancer of the head and neck, esophageal cancer and hepatocellular cancer cells ( 6 , 8 , 20 , 21 ). Notably, ESM1 expression has been demonstrated to be increased in the vascular endothelial cells of prolactinoma and gastric cancer, indicating its involvement in tumor angiogenesis ( 22 , 23 ).…”

“…As a novel marker of cancer, ESM1 has been studied extensively. Research has shown that ESM1 is involved in the process of tumor development in two ways: Firstly, it is abnormally expressed in cancer cells and participates in tumor cell proliferation, migration and invasion ( 6 , 8 , 20 , 21 ); secondly, its expression is increased in vascular endothelial cells, which is associated with the promotion of cancer angiogenesis ( 22 , 23 ). Most of these findings have been obtained from experiments using cells or animals.…”

“…However, under pathological conditions, ESM1 is aberrantly expressed and interacts with its substrate proteins to promote abnormal cell adhesion, proliferation and angiogenesis (5). During tumor development, ESM1 is sporadically expressed in tumor cells and upregulated in tumor vascular endothelial cells, thereby modulating angiogenesis (6)(7)(8)(9)(10).…”

ESM1 May Be Used as a New Indicator for the Diagnosis and Prognosis of Early and Advanced Stage Digestive Tract Cancers

“… 12 Besides, a recent study indicates that ESM1 promotes the occurrence and development of ESCA, and promotes the malignant behavior of esophageal cancer cells. 13 However, the effects of ESM1 on STAD have not been investigated.…”