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Integration of Chemoinformatics and Multi-Omics Analysis Defines ECT2 as a Potential Target for Cancer Drug Therapy

SIMPLE SUMMARY: Cancer is a leading cause of death worldwide and continuous efforts are exerted to develop novel biomarkers and therapeutic agents that could help in early diagnosis and treatment. Analysis of a pan-cancer model that includes a list of human tumors could provide us with a global solu...

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Detalles Bibliográficos
Autores principales: Soltan, Mohamed A., Eldeen, Muhammad Alaa, Sajer, Bayan H., Abdelhameed, Reda F. A., Al-Salmi, Fawziah A., Fayad, Eman, Jafri, Ibrahim, Ahmed, Hebatallah Emam Mohammed, Eid, Refaat A., Hassan, Hesham M., Al-Shraim, Mubarak, Negm, Amr, Noreldin, Ahmed E., Darwish, Khaled M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10135641/
https://www.ncbi.nlm.nih.gov/pubmed/37106813
http://dx.doi.org/10.3390/biology12040613
Descripción
Sumario:SIMPLE SUMMARY: Cancer is a leading cause of death worldwide and continuous efforts are exerted to develop novel biomarkers and therapeutic agents that could help in early diagnosis and treatment. Analysis of a pan-cancer model that includes a list of human tumors could provide us with a global solution to the heterogeneous condition of human cancers. One of the basic approaches for the detection of potential tumor biomarkers and drug targets is the assessment of specific proteins that show upregulation in cancerous tissues versus normal ones. We showed that ECT2 could be considered as a prognostic and immunological biomarker in a list of human cancers through the investigation of several databases. We also employed a chemoinformatics approach to analyze potential inhibitors for ECT2 that could finally act as antitumor agents. ABSTRACT: Epithelial cell transforming 2 (ECT2) is a potential oncogene and a number of recent studies have correlated it with the progression of several human cancers. Despite this elevated attention for ECT2 in oncology-related reports, there is no collective study to combine and integrate the expression and oncogenic behavior of ECT2 in a panel of human cancers. The current study started with a differential expression analysis of ECT2 in cancerous versus normal tissue. Following that, the study asked for the correlation between ECT2 upregulation and tumor stage, grade, and metastasis, along with its effect on patient survival. Moreover, the methylation and phosphorylation status of ECT2 in tumor versus normal tissue was assessed, in addition to the investigation of the ECT2 effect on the immune cell infiltration in the tumor microenvironment. The current study revealed that ECT2 was upregulated as mRNA and protein levels in a list of human tumors, a feature that allowed for the increased filtration of myeloid-derived suppressor cells (MDSC) and decreased the level of natural killer T (NKT) cells, which ultimately led to a poor prognosis survival. Lastly, we screened for several drugs that could inhibit ECT2 and act as antitumor agents. Collectively, this study nominated ECT2 as a prognostic and immunological biomarker, with reported inhibitors that represent potential antitumor drugs.