Utility of ankyrin 3 as a prognostic marker in androgen-receptor-positive breast cancer

Kurozumi, Sasagu; Joseph, Chitra; Raafat, Sara; Sonbul, Sultan; Kariri, Yousif; Alsaeed, Sami; Pigera, Marian; Alsaleem, Mansour; Nolan, Christopher C.; Johnston, Steven J.; Aleskandarany, Mohammed A.; Ogden, Angela; Fujii, Takaaki; Shirabe, Ken; Martin, Stewart G.; Alshankyty, Ibraheem M.; Mongan, Nigel P.; Ellis, Ian O.; Green, Andrew; Rakha, Emad A.

doi:10.1007/s10549-019-05216-w

Cited by 9 publications

(13 citation statements)

References 54 publications

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“…The specificity of the LCN2 antibody (LS-C405956; Lifespan Biosciences, Seattle, WA) (dilution: 1:500) was validated, and a specific band (70 kDa) was detected through western blotting of lysate obtained from the cell line HeLa (The American Type Culture Collection, Rockville, MD) (Supplementary Fig 1). Full-face tissue sections from patients with invasive breast cancer (n = 10) [24][25][26] were stained before tissue microarray (TMA) to assess the morphological characteristics of LCN2 expression and test the suitability of this method. TMA sections from the discovery and validation sets were IHC-stained to evaluate the expression of LCN2 protein.…”

Section: Immunohistochemistrymentioning

confidence: 99%

Clinicopathological significance of lipocalin 2 nuclear expression in invasive breast cancer

Kurozumi

Alsaeed

Orah

et al. 2019

Breast Cancer Res Treat

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PURPOSE:The epithelial-mesenchymal transition (EMT) plays a key role in breast cancer progression and metastasis. Lipocalin 2 (LCN2) is involved in the regulation of EMT. The aim of this study was to investigate the clinicopathological significance of LCN2 expression in breast cancer. METHODS:The expression of LCN2 protein was immunohistochemically assessed in two well-characterised annotated cohorts of breast cancer (discovery cohort, n = 612; validation cohort, n = 1,363). The relationship of LCN2 expression and subcellular location with the clinicopathological factors and outcomes of patients was analysed.RESULTS: Absent or reduced nuclear LCN2 expression was associated with features of aggressive behaviour, including high histological grade, high Nottingham Prognostic Index, high Ki67 labelling index, hormone receptor negativity and human epidermal growth factor receptor 2 positivity. The high cytoplasmic expression of LCN2 was correlated with lymph node positivity. The nuclear downregulation of LCN2 was correlated with the overexpression of EMT associated proteins (N-cadherin and Twist-related protein 2) and basal biomarkers (cytokeratin 5/6 and epidermal growth factor receptor). Unlike the cytoplasmic expression of LCN2, the loss of nuclear expression was a significant predictor of poor outcome. The combinatorial expression tumours with high cytoplasmic and low nuclear expression were associated with the worst prognosis.CONCLUSIONS: Tumour cell expression of LCN2 plays a role in breast cancer progression with loss of its nuclear expression is associated with aggressive features and poor outcome. Further functional analysis is warranted to confirm the relationship between the subcellular localisation LCN2 and behaviour of breast cancer.

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Section: Immunohistochemistrymentioning

confidence: 99%

Clinicopathological significance of lipocalin 2 nuclear expression in invasive breast cancer

Kurozumi

Alsaeed

Orah

et al. 2019

Breast Cancer Res Treat

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“…Somatic mutation of GATA3 is associated with clinicopathological features and expression of TCGA in breast cancer patients (30). FANCD2 (31), DAB1 (32) and ANK3 (33) are all supported by literature to be associated with breast cancer.…”

Section: Tmb Analysismentioning

confidence: 85%

HAUS5 Is A Potential Prognostic Biomarker With Functional Significance in Breast Cancer

et al. 2022

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BackgroundBreast cancer (BRCA) has become the most frequently appearing, lethal, and aggressive cancer with increasing morbidity and mortality. Previously, it was discovered that the HAUS5 protein is involved in centrosome integrity, spindle assembly, and the completion of the cytoplasmic division process during mitosis. By encouraging chromosome misdivision and aneuploidy, HAUS5 has the potential to cause cancer. The significance of HAUS5 in BRCA and the relationship between its expression and clinical outcomes or immune infiltration remains unclear.MethodsPan-cancer was analyzed by TIMER2 web and the expression differential of HAUS5 was discovered. The prognostic value of HAUS5 for BRCA was evaluated with KM plotter and confirmed with Gene Expression Omnibus (GEO) dataset. Following that, we looked at the relationship between the high and low expression groups of HAUS5 and breast cancer clinical indications. Signaling pathways linked to HAUS5 expression were discovered using Gene Set Enrichment Analysis (GSEA). The relative immune cell infiltrations of each sample were assessed using the CIBERSORT algorithm and ESTIMATE method. We evaluated the Tumor Mutation Burden (TMB) value between the two sets of samples with high and low HAUS5 expression, as well as the differences in gene mutations between the two groups. The proliferation changes of BRCA cells after knockdown of HAUS5 were evaluated by fluorescence cell counting and colony formation assay.ResultHAUS5 is strongly expressed in most malignancies, and distinct associations exist between HAUS5 and prognosis in BRCA patients. Upregulated HAUS5 was associated with poor clinicopathological characteristics such as tumor T stage, ER, PR, and HER2 status. mitotic prometaphase, primary immunodeficiency, DNA replication, cell cycle related signaling pathways were all enriched in the presence of elevated HAUS5 expression, according to GSEA analysis. The BRCA microenvironment’s core gene, HAUS5, was shown to be related with invading immune cell subtypes and tumor cell stemness. TMB in the HAUS5-low expression group was significantly higher than that in the high expression group. The mutation frequency of 15 genes was substantially different in the high expression group compared to the low expression group. BRCA cells’ capacity to proliferate was decreased when HAUS5 was knocked down.ConclusionThese findings show that HAUS5 is a positive regulator of BRCA progression that contributes to BRCA cells proliferation. As a result, HAUS5 might be a novel prognostic indicator and therapeutic target for BRCA patients.

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“…Therefore, we speculate that ANK3 mutation might participate in subcellular localization in PTC cells. In contrast, Kurozumi ( 31 ) reported that breast cancer cells showed uniform ANK3 immunoreactivity primarily in the cytoplasm. These results suggested that the different subcellular localization of ANK3 protein is associated with different cancer types.…”

Section: Discussionmentioning

confidence: 95%

“…Several recent studies have reported that ANK3 is strongly associated with bipolar disorder ( 29 , 30 ). Moreover, studies have demonstrated that ANK3 is associated with prostate cancer and breast cancer by regulating the stability of AR ( 31 , 32 ).…”

Section: Resultsmentioning

confidence: 99%

Genetic Alterations in Papillary Thyroid Carcinoma With Hashimoto’s Thyroiditis： ANK3, an Indolent Maintainer of Papillary Thyroid Carcinoma

et al. 2022

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Hashimoto’s thyroiditis (TH) is a risk factor for the occurrence of papillary thyroid carcinoma (PTC), which is considered to be the most common type of thyroid cancer. In recent years, the prevalence of PTC with TH has been increasing, but little is known about the genetic alteration in PTC with TH. This study analyzed the mutation spectrum and mutation signature of somatic single nucleotide variants (SNV) for 10 non-tumor and tumor pair tissues of PTC with TH using whole-exome sequencing. The ANK3 protein expression was evaluated by immunohistochemistry in PTC with TH and PTC samples. Moreover, the functional role of ANK3 in PTC cells was determined by CCK-8 proliferation assay, colony formation assays, cell cycle analysis, cell invasion and migration and in vivo study through overexpression assay. Our results showed three distinct mutational signatures and the C>T/G>A substitution was the most common type of SNV. Gene-set enrichment analysis showed that most of the significantly mutated genes were enriched in the regulation of actin cytoskeleton signaling. Moreover, NCOR2, BPTF, ANK3, and PCSK5 were identified as the significantly mutated genes in PTC with TH, most of which have not been previously characterized. Unexpectedly, it was found that ANK3 was overexpressed in cytoplasm close to the membrane of PTC cells with TH and in almost all PTC cases, suggesting its role as a diagnostic marker of PTC. Ectopic expression of ANK3 suppressed invasion and migration, increased apoptosis of B-CPAP and TPC-1 cells. Moreover, our findings revealed that enhanced ANK3 expression inhibits growth of PTC cells both in vitro and in vivo. Ectopic expression of ANK3 significantly enhanced E-cadherin protein expression and inhibited PTC progression, at least in part, by suppression of epithelial-mesenchymal transition (EMT). Our study shows that ANK3 exerts an anti-oncogenic role in the development of PTC and might be an indolent maintainer of PTC.

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Utility of ankyrin 3 as a prognostic marker in androgen-receptor-positive breast cancer

Cited by 9 publications

References 54 publications

Clinicopathological significance of lipocalin 2 nuclear expression in invasive breast cancer

Clinicopathological significance of lipocalin 2 nuclear expression in invasive breast cancer

HAUS5 Is A Potential Prognostic Biomarker With Functional Significance in Breast Cancer

Genetic Alterations in Papillary Thyroid Carcinoma With Hashimoto’s Thyroiditis： ANK3, an Indolent Maintainer of Papillary Thyroid Carcinoma

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