Suppression of ARID1A associated with decreased CD8 T cells improves cell survival of ovarian clear cell carcinoma
| Autor: | HoHyun Park, Un Suk Jung, Hyung Seok Jang, Kyueng-Whan Min, Dong-Hoon Kim, Mi Jung Kwon |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Vascular Endothelial Growth Factor A
ARID1A Cabozantinib Tumor suppressor gene Cell Survival Adenocarcinoma CD8-Positive T-Lymphocytes Clear Cell 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Translational Research medicine Cytotoxic T cell Humans Ovarian Neoplasms 030219 obstetrics & reproductive medicine business.industry Ovary Obstetrics and Gynecology Nuclear Proteins General Medicine ARID1A Protein medicine.disease Androgen receptor DNA-Binding Proteins Oncology chemistry 030220 oncology & carcinogenesis Clear cell carcinoma Cancer research Original Article Female business Clear cell Human Adenocarcinoma Clear Cell Transcription Factors |
| Zdroj: | Journal of Gynecologic Oncology |
| ISSN: | 2005-0399 2005-0380 |
| Popis: | Objective AT-rich interactive domain 1A (ARID1A) plays an important role as a tumor suppressor gene in ovarian clear cell carcinoma (OCCC), but the clinical application of ARID1A remains unclear. The aim of this study was to analyze clinicopathological parameters, molecular interactions and immune-infiltration in patients with low ARID1A expression and to provide candidate target drugs. Methods We investigated the clinicopathologic parameters, specific gene sets/genes, and immunological relevance according to ARID1A expression in 998 OCCC patients from 12 eligible studies (using meta-analyses); 30 OCCC patients from the Hanyang University Guri Hospital (HYGH) cohort; and 52 OCCC patients from gene set enrichment (GSE) 65986 (25 patients), 63885 (9 patients), and 54809 (6 patients and 12 healthy people) of the Gene Expression Omnibus (GEO). We analyzed network-based pathways based on gene set enrichment analysis (GSEA) and performed in vitro drug screening. Results Low ARID1A expression was associated with poor survival in OCCC from the meta-analysis, HYGH cohort and GEO data. In GSEA, low ARID1A expression was related to the tumor invasion process as well as a low immune-infiltration. In silico cytometry showed that CD8 T cells were decreased with low ARID1A expression. In pathway analysis, ARID1A was associated with angiogenic endothelial cell signaling. In vitro drug screening revealed that cabozantinib and bicalutamide effectively inhibited specific hub genes, such as vascular endothelial growth factor-A and androgen receptor, in OCCC cells with low ARID1A expression. Conclusions Therapeutic strategies making use of low ARID1A could contribute to better clinical management/research for patients with OCCC. |
| Databáze: | OpenAIRE |
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