Abstract
Adrenocortical carcinoma (ACC) is a rare malignant neoplasm that is prone to local invasion and metastasis. Meanwhile, overexpressed endothelial cell-specific molecule 1 (ESM1) is closely related to tumorigenesis of multitudinous tumors. However, the prognosis value and biological function of ESM1 in ACC remains undefined. In the current essay, the assessment in human ACC samples and multiple public cancer databases suggested that ESM1 was significantly overexpressed in ACC patients. The abnormal expression of ESM1 was evidently correlated with dismal overall survival (OS) in ACC patients. Then, the gene-set enrichment analysis (GSEA) was applied to unravel that ESM1 was mostly involved in cell cycle and Notch4 signaling pathway. Furthermore, in vitro experiment, RNA interference of ESM1 was carried out to state that ESM1 augments CDK1 and p21-mediated G2/M-phase transition of mitosis, cell proliferation via DLL4-Notch signaling pathway in human ACC cell line, SW13 cells. Additionally, two possible or available therapeutic strategies, including immunotherapy and chemotherapy, have been further explored. Immune infiltration analysis highlighted that no significant difference was found in ACC patients between EMS1high and EMS1low group for immune checkpoint-related genes. In addition, the overexpression of ESM1 might trigger the accumulation of tumor mutation burden (TMB) during the cell cycle of DNA replication in ACC. The gene-drug interaction network then indicated that ESM1 inhibitors, such as cisplatin, might serve as potential drugs for the therapy of ACC. Collectively, the results asserted that ESM1 and related regulators might act as underlying prognostic biomarkers or novel therapeutic targets for ACC.
Highlights
Adrenocortical carcinoma (ACC) is an aggressive and rare malignant tumor derived from the adrenal cortex and accounting for ~14% of primary adrenal tumor [1]
Adrenocortical adenoma, and ACC, IHC staining suggested that endothelial cell-specific molecule 1 (ESM1) was diffuse cytoplasmic and membrane positive in ACC
In ACC, the combined ESM1 score was significantly higher than that in adrenocortical adenoma and normal adrenal tissues (p < 0.001, Figures 1A, B). It suggested that the ESM1 was strongly expressed in the cytoplasm and membrane of ACC
Summary
Adrenocortical carcinoma (ACC) is an aggressive and rare malignant tumor derived from the adrenal cortex and accounting for ~14% of primary adrenal tumor [1]. The 5-year survival rate is about 35% for ACC with locally advanced stages and less than 28% for ACC with metastases [4, 5]. It indicates that ACC reveals high tumor heterogeneity and harbors a dismal prognosis. Effective therapeutic strategies for the treatment of ACC are scarce. Multiple biomarkers related to the diagnosis, prognosis, or therapy of ACC have been reported. All the research-related above biomarkers of ACC are still in the stage of preclinical research. It is urgent and necessary to uncover potential biomarkers to evaluate the prognostic value in early stage or impolder novel therapeutic strategies
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
