Ovarian Clear Cell Carcinoma Sub-Typing by ARID1A Expression

Choi, Jin; Han, Hyunho; Kim, Young Tae; Lee, Juhyun; Kim, Baek Gil; Kang, Suki; Cho, Nam Hoon

doi:10.3349/ymj.2017.58.1.59

Cited by 14 publications

(8 citation statements)

References 34 publications

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“…Since somatic mutations of ARID1A loss have been frequently identified in OCCC, classified OCCC based on ARID1A expression status also helped to distinguish distinct subtype of OCCC. ARID1A-positive tumors were more likely to be histologically of high grades, ERβ-positive, HNF1β-negative and E-cadherin-negative than ARID1A-negative tumors, but without difference of age, parity, tumor stage and cancer-specific survival 39 . However, BAF250a encoded by ARID1A is a member of the SWI/SNF complex, aggressive behaviors and poor prognosis were observed in the OCCC losing one or multiple SWI/SNF complex subunits 40 .…”

Section: Molecular Classification Of Occcmentioning

confidence: 89%

Updates of Pathogenesis, Diagnostic and Therapeutic Perspectives for Ovarian Clear Cell Carcinoma

Zhu¹,

Xu²,

Zhang³

et al. 2021

J. Cancer

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Ovarian clear cell carcinoma (OCCC) is a special pathological type of epithelial ovarian carcinoma (EOC) and has a high prevalence in Asia without specific molecular subtype classification. Endometriosis is a recognized precancerous lesion that carries 3-fold increased risk of OCCC. Ovarian endometrioid carcinoma, which also originates from endometriosis, shares several features with OCCC, including platinum resistance and younger age at diagnosis. Patients with OCCC have about a 2.5 to 4 times greater risk of having a venous thromboembolism (VTE) compared with other EOC, and OCCC tends to metastasize through lymphatic vesicular and peritoneal spread as opposed to hematogenous metastasis. There is only mild elevation of the conventional biomarker CA125. Staging surgery or optimal cytoreduction combined with chemotherapy is a common therapeutic strategy for OCCC. However, platinum resistance commonly portends a poor prognosis, so novel treatments are urgently needed. Targeted therapy and immunotherapy are currently being studied, including PARP, EZH2, and ATR inhibitors combined with the synthetic lethality of ARID1A-dificiency, and MAPK/PI3K/HER2, VEGF/bFGF/PDGF, HNF1β, and PD-1/PD-L1 inhibitors. Advanced stage, suboptimal cytoreduction, platinum resistance, lymph node metastasis, and VTE are major prognostic predictors for OCCC. We focus on update pathogenesis, diagnostic methods and therapeutic approaches to provide future directions for clinical diagnosis and treatment of OCCC.

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Section: Molecular Classification Of Occcmentioning

confidence: 89%

Updates of Pathogenesis, Diagnostic and Therapeutic Perspectives for Ovarian Clear Cell Carcinoma

Zhu¹,

Xu²,

Zhang³

et al. 2021

J. Cancer

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“…The findings of the relatively limited number of survival analyses conducted to investigate the prognostic value of the ARID1A gene in the outcome of cancer treatment appear to be controversial as well. Actually, relevant studies have reported adverse, beneficial or absolutely no effect of protein loss on the biological behaviour and metastaticity of tumours, the outcome of chemotherapy, the recurrence of cancer, the PFS and the OS of cancer patients, thus clarifying that the abnormal expression of ARID1A affects the prognosis in different ways, mainly depending on the type, stage and grade of the tumour (107,110,117,136).…”

Section: Discussionmentioning

confidence: 99%

“…Four studies on the effects of the mutant gene on the prognosis of ovarian cancer found no significant differences in tumour progression, clinical status and OS between ARID1A protein-positive and -negative patients (127,128,130,136). By contrast, Ayhan et al associated the loss of ARID1A expression with cancer stages I and II and Itamochi et al with a significant reduction of OS of patients at these specific cancer stages (103,119).…”

Section: Summary Of the Findings Of Previous Studies Regarding Arid1a In Cancermentioning

confidence: 99%

Diagnostic significance and prognostic role of the ARID1A gene in cancer outcomes (Review)

Pavlidou

Balis

2020

World Acad Sci J

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Mutations of the ARID1A gene, which encodes the basic directional subunit of SWI/SNF chromatin remodeling complexes, were detected in the middle of the last decade in several cancerous tissue types, highlighting its tumour-suppressive role. Since then, functional studies of the homologous protein have indicated that through its interactions with nucleosomal DNA, transcription factors and nuclear hormone receptors, it plays a key role in regulating cellular proliferation, gene expression and the repair of genetic material, while the loss of its expression triggers carcinogenesis, through mechanisms which have not yet been elucidated. This bibliographic review of clinical investigations focused on the detection of ARID1A mutations and expression levels in malignant tumours, as well as on their association with the prognosis of ARID1A-deficient patients exhibiting a high degree of heterogeneity in the corresponding research findings. The clarification of the prognostic significance of the gene requires further investigation, focusing on cancers and patients of common clinicopathological features. Contents1. Introduction 2. Summary of the materials and methods used for analysis in previous studies 3. Summary of the findings of previous studies regarding ARID1A in cancer 4. Discussion 5. Conclusion and future therapeutic perspectives

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“…Increasing interest has been focused on determining whether the suppression of ARID1A is associated with poor prognosis in patients with OCCC. A study by Previous studies reported that ARID1A deletion was related to worse survival in OCCC [ 12 18 ]. In other studies, no significant difference in survival was found between the absence and presence of ARID1A [ 19 20 ].…”

Section: Introductionmentioning

confidence: 99%

Suppression of ARID1A associated with decreased CD8 T cells improves cell survival of ovarian clear cell carcinoma

et al. 2021

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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 metaanalysis, 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.

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Ovarian Clear Cell Carcinoma Sub-Typing by ARID1A Expression

Cited by 14 publications

References 34 publications

Updates of Pathogenesis, Diagnostic and Therapeutic Perspectives for Ovarian Clear Cell Carcinoma

Updates of Pathogenesis, Diagnostic and Therapeutic Perspectives for Ovarian Clear Cell Carcinoma

Diagnostic significance and prognostic role of the ARID1A gene in cancer outcomes (Review)

Suppression of ARID1A associated with decreased CD8 T cells improves cell survival of ovarian clear cell carcinoma

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