Clinical and biological roles of Kelch-like family member 7 in breast cancer: a marker of poor prognosis

Kurozumi, Sasagu; Joseph, Chitra; Sonbul, Sultan; Gorringe, Kylie L.; Pigera, Marian; Aleskandarany, Mohammed A.; Diez-Rodriguez, Maria; Nolan, Christopher C.; Fujii, Takaaki; Shirabe, Ken; Kuwano, Hiroyuki; Storr, Sarah J.; Martin, Stewart G.; Ellis, Ian O.; Green, Andrew; Rakha, Emad A.

doi:10.1007/s10549-018-4777-z

Cited by 16 publications

(11 citation statements)

References 51 publications

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“…The expression of a large panel of breast cancer progression/metastasis-related biomarkers, including the Ki67 labelling index, E-cadherin, N-cadherin, P-cadherin, Twist-related protein 2 (TWIST2) and basal markers (cytokeratin 5/6 [CK5/6] and epidermal growth factor receptor [EGFR]), was also studied in a previous IHC analysis using the discovery cohort [20][21][22][23][24][25].…”

Section: Patients` Characteristicsmentioning

confidence: 99%

“…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%

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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: Patients` Characteristicsmentioning

confidence: 99%

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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“…External validation was performed using the Breast Cancer Gene-Expression Miner v4.0 (bc-GenExMiner v4.0), 35 as previously described. 33,36 Breast cancer cases data set (n = 818) within The Cancer Genome Atlas (TCGA) 37 was also used for external validation of RXRG mRNA expression. Patient outcome following systemic treatment was further validated using KM Plotter (n = 3951).…”

Section: Study Cohortmentioning

confidence: 99%

Retinoid X receptor gamma (RXRG) is an independent prognostic biomarker in ER-positive invasive breast cancer

et al. 2019

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Background Retinoid X Receptor Gamma (RXRG) is a member of the nuclear receptor superfamily and plays a role in tumour suppression. This study aims to explore the prognostic significance of RXRG in breast cancer. Methods Primary breast cancer tissue microarrays (n = 923) were immuno-stained for RXRG protein and correlated with clinicopathological features, and patient outcome. Results Nuclear RXRG expression was significantly associated with smaller tumour size (p = 0.036), lower grade (p < 0.001), lobular histology (p = 0.016), lower Nottingham Prognostic Index (p = 0.04) and longer breast cancer-specific survival (p < 0.001), and longer time to distant metastasis (p = 0.002). RXRG expression showed positive association with oestrogen receptor (ER)-related biomarkers: GATA3, FOXA1, STAT3 and MED7 (all p < 0.001) and a negative correlation with the Ki67 proliferation marker. Multivariate analysis demonstrated RXRG protein as an independent predictor of longer breast cancer-specific survival and distant metastasis-free survival. In the external validation cohorts, RXRG expression was associated with improved patients’ outcome (p = 0.025). In ER-positive tumours, high expression of RXRG was associated with better patient outcome regardless of adjuvant systemic therapy. ER signalling pathway was the top predicted master regulator of RXRG protein expression (p = 0.005). Conclusion This study provides evidence for the prognostic value of RXRG in breast cancer particularly the ER-positive tumours.

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“…ANK3 protein expression was assessed by IHC using an anti-ANK3 antibody (HPA055643; Merck, Darmstadt, Germany) diluted 1:300 as previously described [38][39][40]. In order to evaluate the pattern of ANK3 protein expression, 15 full-face BC tissue sections were !…”

Section: Ank3 Protein Expressionmentioning

confidence: 99%

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

Kurozumi

Joseph

Raafat

et al. 2019

Breast Cancer Res Treat

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Purpose. Androgen receptor (AR) and AR signaling pathways are thought to play a role in breast cancer (BC) and are potentially related to treatment responses and outcomes. Ankyrin 3 (ANK3) is associated with AR stability in cancer cells. In the present study, we investigated the clinicopathological utility of ANK3 expression with emphasis on AR and its associated signalling pathway at transcriptomic and proteomic phases. Patients and Methods. The Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) cohort (n = 1,980) and The Cancer Genome Atlas (TCGA) dataset (n = 1,039) were used to assess the expression and significance of ANK3 mRNA and other AR signalling pathway-associated gene signature. Using immunohistochemistry, ANK3 protein expression was evaluated in large (n = 982) cohort of early-stage BC with long-term follow-up and compared with clinicopathological characteristics and its prognostic value in the whole cohort and the subgroups stratified by AR protein expression.Results. An AR-related gene signature was developed, comprising 20 genes, which included ANK3. This AR-related gene signature was significantly associated with AR mRNA expression, oestrogen receptor, human epidermal growth factor receptor 2 (HER2) status and the patients' outcomes. In tumours with high AR protein expression (n = 614), high ANK3 protein expression was significantly associated with progesterone receptor positivity and it was independently associated with the good outcomes (p = 0.025).Conclusions. This study indicates that ANK3 is related AR signalling pathway and is associated with BC prognosis.

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Clinical and biological roles of Kelch-like family member 7 in breast cancer: a marker of poor prognosis

Abstract: KLHL7 appears to play an important role in BC progression. High KLHL7 protein expression identified a subgroup of BC with aggressive behaviour and provided independent prognostic information.

Cited by 16 publications

References 51 publications

Clinicopathological significance of lipocalin 2 nuclear expression in invasive breast cancer

Clinicopathological significance of lipocalin 2 nuclear expression in invasive breast cancer

Retinoid X receptor gamma (RXRG) is an independent prognostic biomarker in ER-positive invasive breast cancer

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

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