Splicing imbalances in basal-like breast cancer underpin perturbation of cell surface and oncogenic pathways and are associated with patients’ survival

Gracio, Filipe; Burford, Brian; Gazinska, Patrycja; Mera, Anca; Noor, Aisyah Mohd; Marra, Pierfrancesco; Gillett, Cheryl; Grigoriadis, Anita; Pinder, Sarah; Tutt, Andrew; Rinaldis, Emanuele de

doi:10.1038/srep40177

Cited by 13 publications

(15 citation statements)

References 75 publications

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“…While our paper has been in submission/review and while working on proving the validity of our method, recently another paper was published which performed an analysis similar to our design, but with main focus on basal-like breast tumors 65 . The authors identified ~4500 genes with splicing imbalances between basal-like breast cancer (ER- HER2-) and normal breast samples using exon-arrays.…”

Section: Discussionmentioning

confidence: 99%

Widespread alternative exon usage in clinically distinct subtypes of Invasive Ductal Carcinoma

Bjørklund

Panda

Kumar

et al. 2017

Sci Rep

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Cancer cells can have different patterns of exon usage of individual genes when compared to normal tissue, suggesting that alternative splicing may play a role in shaping the tumor phenotype. The discovery and identification of gene variants has increased dramatically with the introduction of RNA-sequencing technology, which enables whole transcriptome analysis of known, as well as novel isoforms. Here we report alternative splicing and transcriptional events among subtypes of invasive ductal carcinoma in The Cancer Genome Atlas (TCGA) Breast Invasive Carcinoma (BRCA) cohort. Alternative exon usage was widespread, and although common events were shared among three subtypes, ER+ HER2−, ER− HER2−, and HER2+, many events on the exon level were subtype specific. Additional RNA-seq analysis was carried out in an independent cohort of 43 ER+ HER2− and ER− HER2− primary breast tumors, confirming many of the exon events identified in the TCGA cohort. Alternative splicing and transcriptional events detected in five genes, MYO6, EPB41L1, TPD52, IQCG, and ACOX2 were validated by qRT-PCR in a third cohort of 40 ER+ HER2− and ER− HER2− patients, showing that these events were truly subtype specific.

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Section: Discussionmentioning

confidence: 99%

Widespread alternative exon usage in clinically distinct subtypes of Invasive Ductal Carcinoma

Bjørklund

Panda

Kumar

et al. 2017

Sci Rep

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“…However, no such study was carried out yet in this regard, thus in our further studies we will try to address this issue in order to reveal the implications of CCR7 expression. Interestingly, Gracio et al [17]. identified that the CCR7 splicing imbalance was associated with clinical outcomes.…”

Section: Discussionmentioning

confidence: 99%

High Expression of CCR7 Predicts Lymph Node Metastasis and Good Prognosis in Triple Negative Breast Cancer

Sun

et al. 2017

Cell Physiol Biochem

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Background/Aims: Previous preclinical and clinical studies have reported a positive correlation between the expression of the C-C chemokine receptor 7 (CCR7) and the incidence of lymph node metastasis in breast cancer. However, the prognostic relevance of CCR7 expression in breast cancer remains contradictory till now. The aim of this study is to assess the correlation of the CCR7 expression with other clinicopathological features and prognosis in breast cancer. Methods: The CCR7 gene amplification and mRNA expression levels from approximately 3,000 patients were retrieved from human breast cancer databases and analyzed. Furthermore, a total of 188 primary triple negative breast cancer patients were enrolled in this study (diagnosed since January 2009 to January 2013 from the Second Hospital of Dalian Medical University). The protein levels of CCR7 were examined by immunohistochemistry using paraffin-embedded tumor tissues. Results: The analysis of gene amplification and mRNA levels showed the expression of CCR7 in breast cancer correlated with better prognosis. When we compared the CCR7 expressions in different subtypes, the basal-like group showed the highest expression of CCR7 and exhibited a better prognosis. Consistently, Kaplan–Meier analysis of 188 triple negative breast cancer patients showed that the prognosis of patients with positive CCR7 expression was significantly better than those with negative expression (HR=0.642, p=0.0275). Additionally, we also observed a positive correlation between lymph node metastasis and the CCR7 expression (p=0.0096). Conclusions: Our results indicated that elevated CCR7 expression as a marker for increased lymph node metastasis, in addition to serve as an independent prognostic indicator for better overall survival in triple negative breast cancer patients.

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“…One explanation could be that positive CCR7 cancer cells primarily target metastasis to lymph nodes as well as empower the immune system to eliminate escaped cancerous cells [114]. Remarkably, Gracio et al reported that the alternative splicing of CCR7 has been correlated to clinical results [115]. Therefore, the interactions between this essential post-transcriptional regulation and patient survival should be carefully investigated in correlation with CCR7 alternative splicing in breast cancer [116].…”

Section: Ccr7 Expression Is Regulated By Transcription Factors Epigementioning

confidence: 99%

The Role of CCL21/CCR7 Chemokine Axis in Breast Cancer Progression

Rizeq

Malki

2020

Cancers

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Breast cancer is a leading cause of cancer-related deaths worldwide, predominantly caused by metastasis. It is generally accepted that the pattern of breast cancer metastasis is largely determined by the interaction between the chemokine receptors on cancer cells and the chemokines expressed at the sites of metastatic disease. Chemokine receptors belong to the G-protein-coupled receptors (GPCRs) family that appear to be implicated in inflammatory diseases, tumor growth and metastasis. One of its members, C-C Chemokine receptor 7 (CCR7), binds chemokines CCL19 and CCL21, which are important for tissue homeostasis, immune surveillance and tumorigenesis. These receptors have been shown to induce the pathobiology of breast cancer due to their ability to induce cellular proliferation and migration upon the binding of the cognate chemokine receptors. The underlying signaling pathways and exact cellular interactions within this biological system are not fully understood and need further insights. Thus, in this review, we summarize the essential roles of CCR7 and its receptors in breast cancer progression. Furthermore, we discuss the mechanisms of regulation that may lead to novel opportunities for therapeutic intervention. Despite the enormous advances in our knowledge of the nature of the chemokines in breast cancer metastasis, research about the involvement of CCR7 in cancer progression is still limited. Therefore, further studies are essential to illustrate the distinct roles of CCR7 in cancer progression and validate its potential as a preventive bio-factor for human breast cancer metastasis by targeting chemokine receptor genes.

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Splicing imbalances in basal-like breast cancer underpin perturbation of cell surface and oncogenic pathways and are associated with patients’ survival

Cited by 13 publications

References 75 publications

Widespread alternative exon usage in clinically distinct subtypes of Invasive Ductal Carcinoma

Widespread alternative exon usage in clinically distinct subtypes of Invasive Ductal Carcinoma

High Expression of CCR7 Predicts Lymph Node Metastasis and Good Prognosis in Triple Negative Breast Cancer

The Role of CCL21/CCR7 Chemokine Axis in Breast Cancer Progression

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