Pan-cancer analysis of ARID family members as novel biomarkers for immune checkpoint inhibitor therapy

Zhu, Yue; Yan, Chun; Wang, Xiaofei; Xu, Zhijian; Lv, Jianjian; Xu, Xiaomei; Wu, Yu; Yue, Lu

doi:10.1080/15384047.2021.2011643

Cited by 23 publications

(19 citation statements)

References 23 publications

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“…Growing evidence demonstrates that ARID family genes act as tumor promoters or suppressors to regulate the occurrence and development of cancers [8]. A pan-cancer analysis for ARID family members exhibits that ARIDs are novel biomarkers for immune checkpoint inhibitor therapy [12]. ARID1A is highly expressed in primary HCC, and the overexpression of ARID1A could accelerate tumor initiation [31].…”

Section: Discussionmentioning

confidence: 99%

“…In addition, ARID1A silencing promotes epithelial-mesenchymal transition and enhances the sensitivity of pancreatic tumor cells to NVP-AUY922, which is a promising biomarker for the identification of pancreatic ductal adenocarcinomas [ 11 ]. ARID family members are also identified as novel biomarkers for immune checkpoint inhibitor therapy in malignancies by pan-cancer analysis [ 12 ]. Nevertheless, the prognostic value of ARIDs in HCC has not been thoroughly studied.…”

Section: Introductionmentioning

confidence: 99%

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The Prognostic Value of AT-Rich Interaction Domain (ARID) Family Members in Patients with Hepatocellular Carcinoma

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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Objective. Hepatocellular carcinoma (HCC) is one of the most lethal malignancies with a poor prognosis. The AT-rich interaction domain (ARID) family plays an essential regulatory role in the pathogenesis and progression of cancers. This study aims to evaluate the prognostic value and clinical significance of human ARID family genes in HCC. Methods. ONCOMINE and The Cancer Genome Atlas (TCGA) databases were employed to retrieve ARIDs expression profile and clinicopathological information of HCC. Kaplan–Meier plotter and MethSurv were applied to the survival analysis of patients with HCC. CBioPortal was used to analyze genetic mutations of ARIDs. Gene Expression Profiling Interactive Analysis (GEPIA) and Metascape were used to perform hub gene identification and functional enrichment. Results. Expression levels of 11 ARIDs were upregulated in HCC, and 2 ARIDs were downregulated. Also, 4 ARIDs and 5 ARIDs were correlated with pathologic stages and histologic grades, respectively. Furthermore, higher expression of ARID1A, ARID1B, ARID2, ARID3A, ARID3B, ARID5B, KDM5A, KDM5B, KDM5C, and JARID2 was remarkably correlated with worse overall survival of patients with HCC, and the high ARID3C/KDM5D expression was related to longer overall survival. Multivariate Cox analysis indicated that ARID3A, KDM5C, and KDM5D were independent risk factors for HCC prognosis. Moreover, ARIDs mutations and 127 CpGs methylation in all ARIDs were observed to be significantly associated with the prognosis of HCC patients. Besides, our data showed that ARIDs could regulate tumor-related pathways and distinct immune cells in the HCC microenvironment. Conclusions. ARIDs present the potential prognostic value for HCC. Our findings suggest that ARID3A, KDM5C, and KDM5D may be the prognostic biomarkers for patients with HCC.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The Prognostic Value of AT-Rich Interaction Domain (ARID) Family Members in Patients with Hepatocellular Carcinoma

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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“…The AT-rich interaction domain (ARID) family is a superfamily belonging to switch/sucrose nonfermenting (SWI/SNF) chromatin remodeling complexes and the presence of inactivating mutations in any of their members, including ARID5B, has been associated with greater benefit from ICI therapy in pan-cancer analyses [ 22 ]. Conversely, the enrichment of ARID5B expression in HIF-2-altered tumors could suggest innate resistance to ICIs.…”

Section: Discussionmentioning

confidence: 99%

Hypoxia-Inducible Factor-2-Altered Urothelial Carcinoma: Clinical and Genomic Features

et al. 2022

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Background: Hypoxia is recognized as a key feature of cancer growth and is involved in various cellular processes, including proliferation, angiogenesis, and immune surveillance. Besides hypoxia-inducible factor 1-alpha (HIF-1α), which is the main mediator of hypoxia effects and can also be activated under normoxic conditions, little is known about its counterpart, HIF-2. This study focused on investigating the clinical and molecular landscape of HIF-2-altered urothelial carcinoma (UC). Methods: Publicly available next-generation sequencing (NGS) data from muscle-invasive UC cell lines and patient tumor samples from the MSK/TCGA 2020 cohort (n = 476) were interrogated for the level of expression (mRNA, protein) and presence of mutations, copy number variations, structural variants in the EPAS1 gene encoding HIF-2, and findings among various clinical (stage, grade, progression-free and overall survival) and molecular (tumor mutational burden, enriched gene expression) parameters were compared between altered and unaltered tumors. Results: 19% (7/37) of UC cell lines and 7% (27/380) of patients with muscle-invasive UC display high EPAS1 mRNA and protein expression or/and EPAS1 alterations. EPAS1-altered tumors are associated with higher stage, grade, and lymph node metastasis as well as with shorter PFS (14 vs. 51 months, q = 0.01) and OS (15 vs. 55 months, q = 0.01). EPAS1 mRNA expression is directly correlated with that of its target-genes, including VEGF, FLT1, KDR, DLL4, CDH5, ANGPT1 (q < 0.001). While there is a slightly higher tumor mutational burden in EPAS1-altered tumors (9.9 vs. 4.9 mut/Mb), they are enriched in and associated with genes promoting immune evasion, including ARID5B, SPINT1, AAK1, CLIC3, SORT1, SASH1, and FGFR3, respectively (q < 0.001). Conclusions: HIF-2-altered UC has an aggressive clinical and a distinct genomic and immunogenomic profile enriched in angiogenesis- and immune evasion-preventing genes.

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“…Knowledge of chromatin remodeling in the regulation of immunotherapies, especially the immune checkpoint inhibitors (ICIs) in cancer, has yielded several promising therapeutic strategies that show great benefits to patients. Genetic alterations in ARID family members have been revealed to be related to sensitivity to ICI therapy in cancer [ 211 ], such as in NSCLC [ 160 ], EBV-positive gastric cancers [ 212 ], and ovarian cancer ( Figure 4 ) [ 213 , 214 ]. For example, ARID1A alters sensitize tumors to immune checkpoint blockade, suggesting a potential candidate for immunotherapy [ 215 ].…”

Section: Targets For Cancer Therapymentioning

confidence: 99%

Targeting Chromatin-Remodeling Factors in Cancer Cells: Promising Molecules in Cancer Therapy

Zhang

2022

IJMS

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ATP-dependent chromatin-remodeling complexes can reorganize and remodel chromatin and thereby act as important regulator in various cellular processes. Based on considerable studies over the past two decades, it has been confirmed that the abnormal function of chromatin remodeling plays a pivotal role in genome reprogramming for oncogenesis in cancer development and/or resistance to cancer therapy. Recently, exciting progress has been made in the identification of genetic alteration in the genes encoding the chromatin-remodeling complexes associated with tumorigenesis, as well as in our understanding of chromatin-remodeling mechanisms in cancer biology. Here, we present preclinical evidence explaining the signaling mechanisms involving the chromatin-remodeling misregulation-induced cancer cellular processes, including DNA damage signaling, metastasis, angiogenesis, immune signaling, etc. However, even though the cumulative evidence in this field provides promising emerging molecules for therapeutic explorations in cancer, more research is needed to assess the clinical roles of these genetic cancer targets.

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Pan-cancer analysis of ARID family members as novel biomarkers for immune checkpoint inhibitor therapy

Cited by 23 publications

References 23 publications

The Prognostic Value of AT-Rich Interaction Domain (ARID) Family Members in Patients with Hepatocellular Carcinoma

The Prognostic Value of AT-Rich Interaction Domain (ARID) Family Members in Patients with Hepatocellular Carcinoma

Hypoxia-Inducible Factor-2-Altered Urothelial Carcinoma: Clinical and Genomic Features

Targeting Chromatin-Remodeling Factors in Cancer Cells: Promising Molecules in Cancer Therapy

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