EPH/ephrin profile and EPHB2 expression predicts patient survival in breast cancer

Husa, Anna-Maria; Magic, Zeljana; Larsson, Malin; Fornander, Tommy; Pérez-Tenorio, Gizeh

doi:10.18632/oncotarget.7246

Cited by 30 publications

(29 citation statements)

References 42 publications

(54 reference statements)

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“…Reduced expression of EPHB2 29 and PDLIM1 30 are reported to be indicators of poor prognosis of colorectal cancer. Both genes appear to exhibit tissue-specific effects, with upregulation of EPHB2 reported to be associated with poor breast cancer survival31 and elevated expression of PDLIM1 reported to promote metastatic processes in breast and glioma3233. C4BPA and NLRC3 , genes involved in immune processes, are reported to be dysregulated in pancreatic34 and colorectal cancer, respectively35.…”

Section: Discussionmentioning

confidence: 99%

Meta-analysis of gene expression studies in endometrial cancer identifies gene expression profiles associated with aggressive disease and patient outcome

O’Mara

Zhao

Spurdle

2016

Sci Rep

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Although endometrioid endometrial cancer (EEC; comprising ~80% of all endometrial cancers diagnosed) is typically associated with favourable patient outcome, a significant portion (~20%) of women with this subtype will relapse. We hypothesised that gene expression predictors of the more aggressive non-endometrioid endometrial cancers (NEEC) could be used to predict EEC patients with poor prognosis. To explore this hypothesis, we performed meta-analysis of 12 gene expression microarray studies followed by validation using RNA-Seq data from The Cancer Genome Atlas (TCGA) and identified 1,253 genes differentially expressed between EEC and NEEC. Analysis found 121 genes were associated with poor outcome among EEC patients. Forward selection likelihood-based modelling identified a 9-gene signature associated with EEC outcome in our discovery RNA-Seq dataset which remained significant after adjustment for clinical covariates, but was not significant in a smaller RNA-Seq dataset. Our study demonstrates the value of employing meta-analysis to improve the power of gene expression microarray data, and highlight genes and molecular pathways of importance for endometrial cancer therapy.

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Section: Discussionmentioning

confidence: 99%

Meta-analysis of gene expression studies in endometrial cancer identifies gene expression profiles associated with aggressive disease and patient outcome

O’Mara

Zhao

Spurdle

2016

Sci Rep

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“…A series of studies have reported a direct correlation between EPHB2 expression and numerous human malignancies, including NSCLC. EPHB2 activates bidirectional signaling cascades and its upregulation predicts poor survival in LUAD [86], CRC [87], breast cancer [88] and malignant mesothelioma [89]. One study indicated that EPHB2 enhances cellular growth, migration and invasion in CeCa by a competitive inhibition that counteracts the miR-204 effect on cell cycle arrest, Bax overexpression and PI3K/AKT signaling pathway deactivation via competitive inhibition [90].…”

Section: Discussionmentioning

confidence: 99%

Downregulation of hsa-microRNA-204-5p and identification of its potential regulatory network in non-small cell lung cancer: RT-qPCR, bioinformatic- and meta-analyses

Liang

Gan

et al. 2020

Respir Res

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Background: Pulmonary malignant neoplasms have a high worldwide morbidity and mortality, so the study of these malignancies using microRNAs (miRNAs) has attracted great interest and enthusiasm. The aim of this study was to determine the clinical effect of hsa-microRNA-204-5p (miR-204-5p) and its underlying molecular mechanisms in non-small cell lung cancer (NSCLC). Methods: Expression of miR-204-5p was investigated by real-time quantitative PCR (RT-qPCR). After data mining from public online repositories, several integrative assessment methods, including receiver operating characteristic (ROC) curves, hazard ratios (HR) with 95% confidence intervals (95% CI), and comprehensive meta-analyses, were conducted to explore the expression and clinical utility of miR-204-5p. The potential objects regulated and controlled by miR-204-5p in the course of NSCLC were identified by estimated target prediction and analysis. The regulatory network of miR-204-5p, with its target genes and transcription factors (TFs), was structured from database evidence and literature references. Results: The expression of miR-204-5p was downregulated in NSCLC, and the downtrend was related to gender, histological type, vascular invasion, tumor size, clinicopathologic grade and lymph node metastasis (P<0.05). MiR-204-5p was useful in prognosis, but was deemed unsuitable at present as an auxiliary diagnostic or prognostic risk factor for NSCLC due to the lack of statistical significance in meta-analyses and absence of large-scale investigations. Gene enrichment and annotation analyses identified miR-204-5p candidate targets that took part in various genetic activities and biological functions. The predicted TFs, like MAX, MYC, and RUNX1, interfered in regulatory networks involving miR-204-5p and its predicted hub genes, though a modulatory loop or axis of the miRNA-TF-gene that was out of range with shortage in database prediction, experimental proof and literature confirmation. Conclusions: The frequently observed decrease in miR-204-5p was helpful for NSCLC diagnosis. The estimated target genes and TFs contributed to the anti-oncogene effects of miR-204-5p.

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“…(77,81) The Eph receptors/ephrins have also been implicated in tumourigenesis, progression and metastasis across a wide range of malignancies (Table 3). ( (83) Prostate cancer (84,85) Breast cancer (86,87) Melanoma (88) Glioblastoma (89,90) Gastric cancer (91) EphA3 Gastric cancer (92) Colorectal cancer (93) EphB2 Advanced cSCC (94) Glioblastoma (95)(96)(97) Cervical cancer (98) Breast cancer (99) EphB4 HNSCC (100) Non-small cell lung cancer (101) Breast cancer (99) Downregulated EphA1 NMSC (77) …”

Section: Galaninmentioning

confidence: 99%

Molecular mechanisms of perineural spread of cutaneous carcinoma: a potential role for receptor tyrosine kinases and other biomarkers

Schmidt¹

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Perineural invasion and spread of cutaneous squamous cell carcinoma of the head and neck (cSCCHN) is associated with worse prognosis and high rates of locoregional recurrence. It occurs in less than 5% of cases, but given the high incidence of cSCC in Australia, portends significant morbidity and mortality. Primary tumour biology remains poorly understood and precise molecular mechanisms by which malignant squamous cells invade and progress axially within the perineural space remain unclear. Thus, there is no targeted therapy for perineural spread of cSCCHN or other neurotropic malignancies. Dysregulation of cell membrane receptor trafficking is a hallmark of cancer and such receptors are potential therapeutic targets.Over-expression of the epidermal growth factor receptor (EGFR) is well described in squamous cell carcinoma and the monoclonal antibody cetuximab is approved for advanced mucosal head Ultimately, we aim to improve survival and quality of life for sufferers of this morbid form of tumour spread. Our findings may also have implications for other neurotropic malignancy, including pancreatic, gastric, colorectal and prostate cancers. 4 Declaration by authorThis thesis is composed of my original work, and contains no material previously published or written by another person except where due reference has been made in the text. I have clearly stated the contribution by others to jointly-authored works that I have included in my thesis.

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EPH/ephrin profile and EPHB2 expression predicts patient survival in breast cancer

Cited by 30 publications

References 42 publications

Meta-analysis of gene expression studies in endometrial cancer identifies gene expression profiles associated with aggressive disease and patient outcome

Meta-analysis of gene expression studies in endometrial cancer identifies gene expression profiles associated with aggressive disease and patient outcome

Downregulation of hsa-microRNA-204-5p and identification of its potential regulatory network in non-small cell lung cancer: RT-qPCR, bioinformatic- and meta-analyses

Molecular mechanisms of perineural spread of cutaneous carcinoma: a potential role for receptor tyrosine kinases and other biomarkers

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