ANK2 Hypermethylation in Canine Mammary Tumors and Human Breast Cancer

Schabort, Johannes J.; Nam, A-Reum; Lee, Kanghoon; Kim, Seok Won; Lee, Jeong Eon; Cho, Je‐Yoel

doi:10.3390/ijms21228697

Cited by 15 publications

(9 citation statements)

References 55 publications

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“…Concerning ANK2 expression, it has been found to be downregulated in breast cancer and colon adenocarcinoma [30,54], which was consistent with the findings of our pan-cancer analysis. In terms of lung cancer, ANK2 has not been studied and we proved that ANK2 was downregulated in LUAD.…”

Section: Discussionsupporting

confidence: 91%

“…Ying and his colleagues proved that ANK2 was overexpressed in pancreatic ductal adenocarcinoma and inhibition of ANK2 reduced invasion ability of pancreatic cancer cells [27]. Moreover, vital roles of Ankyrins have been observed in gastric cancer, breast cancer, and prostate cancer [28][29][30]. However, the impact of ANK2 (ANK2 mutation and expression) on the prognosis of LUAD patients, especially those treated with ICIs, is unknown.…”

Section: Introductionmentioning

confidence: 99%

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ANK2 as a novel predictive biomarker for immune checkpoint inhibitors and its correlation with antitumor immunity in lung adenocarcinoma

et al. 2022

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Background Immune checkpoint inhibitors (ICIs) have been shown to significantly improve the survival of patients with advanced lung adenocarcinoma (LUAD). However, only limited proportion of patients could benefit from ICIs. Novel biomarkers with strong predictability are needed for clinicians to maximize the efficacy of ICIs. Our study aimed to identify potential biomarkers predicting ICIs efficacy in LUAD. Methods The Cancer Genome Atlas (TCGA) PanCancer Atlas studies in cBioportal were used to evaluate the mutation frequency of ANK2 across multiple cancers. Clinical and mutational data for LUAD from ICIs-treated cohorts (Hellmann et al. and Rizvi et al.) were collected to explore the correlation between ANK2 mutation and clinical outcomes. In addition, the relationship between ANK2 expression and clinical outcomes was analyzed using LUAD data from TCGA and Gene Expression Omnibus. Furthermore, the impact of ANK2 mutation and expression on the tumor immune microenvironment of LUAD was analyzed using TCGA and TISIDB databases. Results Patients with ANK2 mutation benefited more from ICIs. In ICIs-treated cohort, prolonged progression-free survival (PFS) (median PFS: NR (not reached) vs. 5.42 months, HR (hazard ratio) 0.31, 95% CI 0.18–0.54; P = 0.0037), improved complete response rate (17.65% vs. 1.85%, P = 0.0402), and improved objective response rate (64.71% vs. 24.07%, P = 0.0033) were observed in LUAD patients with ANK2 mutation compared to their wild-type counterparts. Regarding ANK2 expression, it was observed that ANK2 expression was decreased in LUAD (P < 0.05) and a higher level of ANK2 expression was associated with longer overall survival (HR 0.69, 95% CI 0.52–0.92; P = 0.012) in TCGA LUAD cohort. Moreover, ANK2 mutation or higher ANK2 expression correlated with enhanced antitumor immunity and “hot” tumor microenvironment in LUAD, which could be potential mechanisms that ANK2 mutation facilitated ICIs therapy and patients with higher ANK2 expression survived longer. Conclusion Our findings suggest that ANK2 mutation or increased ANK2 expression may serve as a favorable biomarker for the efficacy of ICIs in patients with LUAD.

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Section: Discussionsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

ANK2 as a novel predictive biomarker for immune checkpoint inhibitors and its correlation with antitumor immunity in lung adenocarcinoma

et al. 2022

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“…We designed bisul te primers using the Bisul te Primer Seeker (https://www.zymoresearch.com/pages/bisul te-primer-seeker). The overall process of targeted BS-seq was conducted as previously described [49]. The primer sequences are listed in Table S10).…”

Section: Functional Enrichment Analysismentioning

confidence: 99%

Machine learning-based tumor malignancy prediction based on PBMC methylome landscape in canine mammary tumor

Nam

Heo

Lee

et al. 2023

Preprint

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Background Genome-wide dysregulation of CpG methylation accompanies tumor progression and characteristic states of cancer cells, prompting a rationale for biomarker development. Understanding how the archetypic epigenetic modification determines systemic contributions of immune cell types is the key to further clinical benefits. Results In this study, we characterized the differential DNA methylome landscapes of peripheral blood mononuclear cells (PBMCs) from 76 canines using methylated CpG-binding domain sequencing (MBD-seq). Through gene set enrichment analysis, we discovered that genes involved in the growth and differentiation of T- and B-cells are highly methylated in tumor PBMCs. We also revealed the increased methylation at single CpG resolution and reversed expression in representative marker genes regulating immune cell proliferation (BACH2, SH2D1A, TXK, UHRF1). Furthermore, we utilized the PBMC methylome to effectively differentiate between benign and malignant tumors and the presence of mammary gland tumors through a machine-learning approach. Conclusions This research contributes to a better knowledge of the comprehensive epigenetic regulation of circulating immune cells responding to tumors and suggests a new framework for identifying benign and malignant cancers using genome-wide methylome.

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“…A similar approach using the identification of DMRs to map genes subject to methylation modulation was applied by Schabort et al (2020 ), which resulted in a mapping of 16,061 differentially methylated genes. Among them, two genes, ANK2 and EPAS1 , were observed to have a high level of hypermethylation in tumoral tissues compared with normal samples.…”

Section: Dna Methylationmentioning

confidence: 99%

Epigenetic alterations in canine mammary cancer

Borges

2022

Genet. Mol. Biol.

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In dogs, mammary cancer is the most common tumor type, especially in unspayed females. As in humans, this type of cancer has spontaneous development and is influenced by several risk factors, such as age and hormonal exposure in addition to genetic and epigenetic factors. Epigenetic mechanisms are responsible for gene expression modulation without alterations in the DNA sequence and include but are not limited to DNA methylation, histone modifications, and noncoding RNAs. Epigenetic patterns are known to influence a variety of biological mechanisms, such as cellular differentiation and development, and dysregulations of those patterns may result in several diseases, such as cancer. In this respect, this review summarizes the main findings concerning epigenetic alterations in canine mammary cancer, their relationship with the carcinogenic process, and their use as diagnostic and prognostic markers.

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ANK2 Hypermethylation in Canine Mammary Tumors and Human Breast Cancer

Cited by 15 publications

References 55 publications

ANK2 as a novel predictive biomarker for immune checkpoint inhibitors and its correlation with antitumor immunity in lung adenocarcinoma

ANK2 as a novel predictive biomarker for immune checkpoint inhibitors and its correlation with antitumor immunity in lung adenocarcinoma

Machine learning-based tumor malignancy prediction based on PBMC methylome landscape in canine mammary tumor

Epigenetic alterations in canine mammary cancer

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