Comprehensive analysis of multiple parameters associated with tumor immune microenvironment in
            <i>ARID1A</i>
            mutant cancers

Li, Zhenxiang; Lin, Jiamao; Zhang, Lijuan; Li, Jingchao; Zhang, Yingyun; Zhao, Chen

doi:10.2217/fon-2020-0243

Cited by 7 publications

(4 citation statements)

References 41 publications

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“…This finding was consistent with the findings of previous studies that reported ARID1A mutations to be related to the high immune infiltrates in endometrial cancer and that their results revealed ARID1A-deficient tumors to display increased CD8+ TILs (44,59,60) . In another work, ARID1A loss was found to be associated with MMRd (p<0.001) and found highly significant association between MMRd and increasing CD8+ TIL density…”

Section: Combined Arid1a and Cd8+ Expression In Relation To Patient S...supporting

confidence: 93%

The Diagnostic and Prognostic Significance of ARID1A and CD8+ Expression in Endometrial Hyperplasia and Endometrial Endometrioid Adenocarcinoma (Immunohistochemical study)

Sawi

Hassan²,

Youssef³

et al. 2022

Benha Medical Journal

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Background: Epigenetic driver mutations and tumor microenvironment could play an important and promising role in diagnosis, prognosis, and prediction of different endometrial lesions. Aim: To determine their putative diagnostic and prognostic value, this work analyzes the immunohistochemical (IHC) expression of ARID1A and CD8+ in endometrial hyperplasia (EH) and endometrioid endometrial adenocarcinoma (EEA). Material and methods: The 80 distinct endometrial lesions included in this retrospective study included (20) EH without atypia, (30) atypical EH (AEH), and (30) EEA. Clinicopathological characteristics and survival of examined cases were correlated with the IHC expression of ARID1A and CD8+. Results: ARID1A negative expression was significantly associated with EEA (46.7%) and AEH (30%), while its positivity was associated with EH without atypia cases (100%) (P<0.01). ARID1A showed 100% specificity and 38.3% sensitivity for premalignant (AEH) and malignant lesions. When compared to normal endometrium and EH without atypia, the amount of intraepithelial and stromal CD8+ expression revealed a significant difference between the examined cases (P<0.01 and P<0.05, respectively). ARID1A loss and high CD8+ expression was shown to be significantly correlated (P<0.01). Longer disease-free and recurrence-free survival were linked to ARID1A loss and high CD8+ expression. There was no discernible relationship between tumor grade, histologic type, lympho-vascular invasion, lymph node metastasis, or FIGO stage and either ARID1A or CD8+. Conclusion: ARID1A can be a reliable diagnostic indicator for premalignant lesions. ARID1A and CD8+ can each independently indicate a patient's increased chance of living longer and serve as biomarkers for the effectiveness of immunotherapy.

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Section: Combined Arid1a and Cd8+ Expression In Relation To Patient S...supporting

confidence: 93%

The Diagnostic and Prognostic Significance of ARID1A and CD8+ Expression in Endometrial Hyperplasia and Endometrial Endometrioid Adenocarcinoma (Immunohistochemical study)

Sawi

Hassan²,

Youssef³

et al. 2022

Benha Medical Journal

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“…They indicated that TET1 mutation was closely associated with higher NAL, presenting a higher objective response rate, better durable clinical benefit, longer progression-free survival (PFS), and improved OS in patients receiving ICIs (47). A series of studies have shown the relationship between genetic mutations and NAL, such as TP53-MT (43), Eph receptor A5 mutations (48), ZFHX3-MT (49), and AT-rich interaction domain 1A (50), which are closely related to longer OS or PFS in patients treated with ICIs.…”

Section: Nal and Genomic Alterationsmentioning

confidence: 99%

Prognostic Value of Neoantigen Load in Immune Checkpoint Inhibitor Therapy for Cancer

Zou

et al. 2021

Front. Immunol.

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Immune checkpoint inhibitors (ICIs) have made great progress in the field of tumors and have become a promising direction of tumor treatment. With advancements in genomics and bioinformatics technology, it is possible to individually analyze the neoantigens produced by somatic mutations of each patient. Neoantigen load (NAL), a promising biomarker for predicting the efficacy of ICIs, has been extensively studied. This article reviews the research progress on NAL as a biomarker for predicting the anti-tumor effects of ICI. First, we provide a definition of NAL, and summarize the detection methods, and their relationship with tumor mutation burden. In addition, we describe the common genomic sources of NAL. Finally, we review the predictive value of NAL as a tumor prediction marker based on various clinical studies. This review focuses on the predictive ability of NAL’s ICI efficacy against tumors. In melanoma, lung cancer, and gynecological tumors, NAL can be considered a predictor of treatment efficacy. In contrast, the use of NAL for urinary system and liver tumors requires further research. When NAL alone is insufficient to predict efficacy, its combination with other indicators can improve prediction efficiency. Evaluating the response of predictive biomarkers before the treatment initiation is essential for guiding the clinical treatment of cancer. The predictive power of NAL has great potential; however, it needs to be based on more accurate sequencing platforms and technologies.

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“…Loss of ARID1A was found to have a significant correlation with the expression of IFN-g and checkpoint genes (including PD-L1, CTLA4, and PDCD1) in microsatellite-stable colorectal cancer (29). In addition, ARID1A has been proven to serve as a biomarker for the sensitivity to immune checkpoint inhibitors (29)(30)(31)(32).…”

Section: Discussionmentioning

confidence: 99%

ARID1A Downregulation Predicts High PD-L1 Expression and Worse Clinical Outcome in Patients With Gallbladder Cancer

Nan

Wang

et al. 2022

Front. Oncol.

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BackgroundRecent studies have confirmed that AT-rich interactive domain-containing protein 1A (ARID1A) plays a critical role in tumorigenesis, but its role in gallbladder cancer (GBC) remains unclear.MethodsIn total, 224 patients from Zhongshan Hospital were recruited for this retrospective study. The clinicopathological and baseline characteristics of the patients were collected. Bioinformatics analysis was performed to reveal variations in genes and signaling pathways, and ARID1A and PD-L1 expression and the number of PD1+ tumor-infiltrating lymphocytes (TILs) were measured by immunohistochemical staining.ResultsARID1A expression was negatively correlated with overall survival in patients with GBC, and multivariate analysis identified ARID1A as an independent prognostic factor for overall survival. A heatmap and gene set enrichment analysis suggested that cytotoxic T lymphocyte signatures and immune-related signaling pathways were downregulated in ARID1A low tumors. Subsequent immunohistochemical staining confirmed that ARID1A expression was negatively correlated with PD-L1 expression and PD1+ TILs in the tumor microenvironment. The Kaplan–Meier analysis suggested that high ARID1A expression combined with low PD-L1 expression or low PD1+ TIL counts is associated with the best prognosis in patients with GBC.ConclusionARID1A inactivation can lead to a worse prognosis in patients with GBC, potentially by mediating immune evasion through the PD1/PD-L1 pathway.

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Comprehensive analysis of multiple parameters associated with tumor immune microenvironment in ARID1A mutant cancers

Cited by 7 publications

References 41 publications

The Diagnostic and Prognostic Significance of ARID1A and CD8+ Expression in Endometrial Hyperplasia and Endometrial Endometrioid Adenocarcinoma (Immunohistochemical study)

The Diagnostic and Prognostic Significance of ARID1A and CD8+ Expression in Endometrial Hyperplasia and Endometrial Endometrioid Adenocarcinoma (Immunohistochemical study)

Prognostic Value of Neoantigen Load in Immune Checkpoint Inhibitor Therapy for Cancer

ARID1A Downregulation Predicts High PD-L1 Expression and Worse Clinical Outcome in Patients With Gallbladder Cancer

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