Clinicopathological and prognostic significance of Ras association and pleckstrin homology domains 1 (RAPH1) in breast cancer

Kurozumi, Sasagu; Joseph, Chitra; Sonbul, Sultan; Aleskandarany, Mohammed A.; Pigera, Marian; Alsaleem, Mansour; Alsaeed, Sami; Kariri, Yousif; Nolan, Christopher C.; Diez-Rodriguez, Maria; Johnston, Steven J.; Mongan, Nigel P.; Fujii, Takaaki; Shirabe, Ken; Martin, Stewart G.; Ellis, Ian O.; Green, Andrew; Rakha, Emad A.

doi:10.1007/s10549-018-4891-y

Cited by 10 publications

(9 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…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%

See 1 more Smart Citation

Clinicopathological significance of lipocalin 2 nuclear expression in invasive breast cancer

Kurozumi

Alsaeed

Orah

et al. 2019

Breast Cancer Res Treat

Self Cite

View full text Add to dashboard Cite

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.

show abstract

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

Self Cite

View full text Add to dashboard Cite

show abstract

“…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

Self Cite

View full text Add to dashboard Cite

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.

show abstract

“…We therefore performed low-input RNA-seq in resting total CD4 + T cells from 24 healthy subjects with 8 A/A, 8 A/C, and 8 C/C genotypes at rs117701653 and analyzed association with expression of all 11 protein-coding genes lying within 1Mb of the SNP. Surprisingly, expression of CD28 and CTLA4 did not vary with genotype, nor did RAPH1 , another nearby gene 26 . Instead, allelic variation at rs117701653 correlated strongly with expression of ICOS , located 173kb 3’ (β=–22.4 and p=0.0051 by linear regression with adjustment for age, sex, and multiple testing) ( Fig.…”

Section: Resultsmentioning

confidence: 80%

Non-coding autoimmune risk variant accelerates T peripheral helper cell development via ICOS

Kim

Martínez‐Bonet

Wang

et al. 2022

Preprint

View full text Add to dashboard Cite

Fine-mapping and functional studies implicate rs117701653, a common non-coding variant in the CD28/CTLA4/ICOS locus, as a contributor to risk for rheumatoid arthritis and type 1 diabetes. Using DNA pulldown, mass spectrometry, genome editing and eQTL analysis, we establish that the disease-associated allele reduces affinity for the inhibitory chromosomal regulator SMCHD1 to drive expression of inducible T-cell costimulator (ICOS), enhancing memory CD4+ T cell ICOS expression in individuals bearing the risk allele. Higher ICOS expression is paralleled by an increase in circulating T peripheral helper (Tph) cells, and in rheumatoid arthritis patients, of blood and joint fluid Tph cells and circulating plasmablasts, suggesting a causal link. Indeed, ICOS ligation accelerates T cell differentiation into CXCR5-PD-1high Tph cells producing IL-21 and CXCL13, as does carriage of the rs117701653 risk allele. Thus, mechanistic dissection of a causal non-coding variant in human autoimmunity discloses a new pathway through which ICOS regulates Tph abundance.

show abstract

Clinicopathological and prognostic significance of Ras association and pleckstrin homology domains 1 (RAPH1) in breast cancer

Abstract: High RAPH1 expression is correlated with aggressive breast cancer phenotypes and provides independent prognostic value in invasive breast cancer.

Cited by 10 publications

References 40 publications

Clinicopathological significance of lipocalin 2 nuclear expression in invasive breast cancer

Clinicopathological significance of lipocalin 2 nuclear expression in invasive breast cancer

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

Non-coding autoimmune risk variant accelerates T peripheral helper cell development via ICOS

Contact Info

Product

Resources

About