Hypoxia inducible factor 1α gene (HIF-1α) splice variants: potential prognostic biomarkers in breast cancer

Dalès, Jean-Philippe; Beaufils, Nathalie; Silvy, Monique; Picard, Christophe; Pauly, Vanessa; Pradel, Vincent; Formisano-Tréziny, Christine; Bonnier, Pascal; Giusiano, Sophie; Charpin, Colette; Gabert, Jean

doi:10.1186/1741-7015-8-44

Cited by 47 publications

(40 citation statements)

References 33 publications

(47 reference statements)

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“…[28][29][30][31][32] However, our results showed an important correlation between the expression of HIF-1a and cell proliferation. In addition, we found that the expression of HIF-1a was in part dependent on glycolysis, suggesting that in the early stages of MF, the synthesis of HIF-1a is at least partially dependent on proliferating T cells that follow a glycolytic pathway instead of oxidative phosphorylation.…”

contrasting

confidence: 52%

“…27 In malignant tissues, HIF-1a regulates cellular metabolism and the transcription of cytokines and growth factors associated with malignant neoplasias. [28][29][30][31] In several studies, the increased expression of HIF-1a has been correlated with the progression, aggressiveness and poor prognosis of numerous types of cancer, including lymphoma. 26,32 In addition, there is evidence that HIF-1a can negatively regulate the T-cell response.…”

Section: Mycosis Fungoides (Mf) Is the Most Common Clinical Variant Omentioning

confidence: 99%

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Overexpression of hypoxia‐inducible factor 1 alpha impacts FoxP3 levels in mycosis fungoides—Cutaneous T‐cell lymphoma: Clinical implications

Alcántara‐Hernández

Torres-Zárate

Pérez-Montesinos³

et al. 2013

Intl Journal of Cancer

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Mycosis fungoides (MF) is the most common variant of primary cutaneous T‐cell lymphoma, and decreased forkhead box P3 (FoxP3) expression has been reported in MF late stages. Hypoxia‐inducible factor 1 alpha (HIF‐1α) may regulate FoxP3 expression; however, it is unknown whether HIF‐1α is expressed in the CD4+ T cells of MF patients and how it could affect the expression of FoxP3. Therefore, we evaluated the expression of HIF‐1α and FoxP3 in CD4+ T cells obtained from the skin lesions of MF patients. We found increased cell proliferation and an increase in CD4+ T cells with an aberrant phenotype among early stage MF patients. HIF‐1α was overexpressed in these CD4+ T cells. In addition, we found a decrease in the percentage of FoxP3+ cells both in the skin of MF patients, when compared with control skin samples, and with disease progression. In addition, a negative correlation was established between HIF‐1α and FoxP3 expression. Skin HIF‐1α expression in MF patients correlated with the extent of the affected area and increased with the disease progression. Finally, we showed that ex vivo inhibition of HIF‐1α degradation increases the percentage of FoxP3+ T cells in skin lesions. Our results suggest that overexpression of HIF‐1α affects the levels of FoxP3 in MF patients, which could have relevant implications in terms of disease outcome.

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confidence: 52%

Section: Mycosis Fungoides (Mf) Is the Most Common Clinical Variant Omentioning

confidence: 99%

Overexpression of hypoxia‐inducible factor 1 alpha impacts FoxP3 levels in mycosis fungoides—Cutaneous T‐cell lymphoma: Clinical implications

Alcántara‐Hernández

Torres-Zárate

Pérez-Montesinos³

et al. 2013

Intl Journal of Cancer

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“…RNA was isolated using the RNeasy Mini Kit (Qiagen, Hilden, Germany), according to the manufacturer's instructions. Real-time PCR (primer and probe) for HIF1a was performed as previously described by Dales et al 14 Abl quantified by real-time PCR as published earlier was used as housekeeping gene. 15 Quantification of RNA transcript expression was normalized determining the ratio between expression levels of targets and Abl.…”

Section: Methodsmentioning

confidence: 99%

Bronchiolitis obliterans after allogeneic hematopoietic SCT: further insight—new perspectives?

Ditschkowski

Elmaagacli

Koldehoff

et al. 2013

Bone Marrow Transplant

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Bronchiolitis obliterans (BO) is a late non-infectious pulmonary complication after allogeneic hematopoietic SCT. Among 982 patients after myeloablative hematopoietic SCT between January 2000 and October 2010, 68 were diagnosed with BO according to NIH criteria. The median onset of BO was 18 months post transplant, 5-year cumulative incidence was 5.8% and 5-year mortality 41%. BO prevalence rate was 10% among all long-term surviving hematopoietic SCT recipients and 12% among chronic GVHDpatients. Chronic GVHD, peripheral SCT and ABO blood group incompatibility were identified as risk factors associated with BO. IgG levels were significantly decreased at the onset of BO (6.7 g/L ± 0.7, P ¼ 0.001), the mean exhaled NO concentrations were lower in BO-patients than in stem cell recipients without BO (14 p.p.b.±0.9 vs 20 p.p.b.±2.1) or healthy controls (25 p.p.b.±2.4, Po0.001). Hypoxia-inducible factor 1 alpha (HIF-1a) was significantly elevated in BO as compared with healthy controls or GVHD-patients without lung involvement (340 ± 61 vs 127 ± 22 vs 140 ± 32, P ¼ 0.02). Calculated 5-year survival was superior in female than in male BO-patients (86 vs 45%, P ¼ 0.04). These results emphasize the relevance of BO as serious late complication with substantial mortality and point to essential pathophysiological changes due to regulatory responses to hypoxia. Keywords: bronchiolitis obliterans; nitric oxide; allogeneic; GVHD; HIF-1a; SCT INTRODUCTION Allogeneic hematopoietic SCT has been shown to provide longterm disease-free survival for otherwise fatal malignant or nonmalignant hematological disorders. With increasing survival rates due to toxicity reduced hematopoietic SCT methods, advanced GVHD-management and improved anti-infectious therapy and prophylaxis, a distinct increment in late transplant related complications can be observed. Pulmonary complications develop in 30-60% of allogeneic hematopoietic SCT recipients and are considered as a major cause of morbidity and mortality. 1,2 Late-onset non-infectious pulmonary complications 3 beginning 3 months after transplantation with an incidence of 10-15% are considered as life-threatening complications significantly limiting the quality of life. 4,5 Although late-onset non-infectious pulmonary complications classification is rather undefined, the most common categorizations include bronchiolitis obliterans (BO), bronchiolitis obliterans organizing pneumonia and interstitial pneumonia. 6,7 According to the NIH consensus criteria, BO is considered to be the only pulmonary manifestation of chronic GVHD. 8 The reported incidence of BO in allogeneic hematopoietic SCT recipients ranges from 2-10% and mortality rates have been assessed between 13 and 23%. 9,10 BO is prevalent in 2-5.5% of hematopoietic SCT recipients and in up to 14% of hematopoietic SCT recipients with chronic GVHD. 11 Patients diagnosed with BO have a 5-year survival rate of only 45% vs 75% in patients without BO. 9 Advanced disease stages at transplantation, preceding GVHD, older donor and recipient age, M...

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“…On the other hand, Zhang and co-workers showed that EBV miRNAs (miR-BART7 and miR-BART13) can serve as important biomarkers for NPC diagnosis and prediction of treatment efficacy [58]. The potential prognostic value of EGFR and HIF1α has been previously demonstrated in breast and prostate cancers [60,61]. It would be interesting if these proteins can also be used as prognostic markers for EBV-related cancers.…”

Section: Novel Implications Of Exosomes In Diagnosis and Treatment Ofmentioning

confidence: 99%

Exosomes as the Promising Biomarker for Epstein-Barr Virus (EBV)-Associated Cancers

Teow¹,

Peh²

2017

Novel Implications of Exosomes in Diagnosis and Treatment of Cancer and Infectious Diseases

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Exosomes are microvesicles with sizes ranging from 50 to 150 nm. These small vesicles are known to morphologically and functionally resemble virus particles from human immunodeficiency virus type I (HIV-I) and human T-lymphotropic virus type I (HTLV-I). The function of exosomes is to mainly mediate cell-to-cell communication by exchanging various macromolecules including proteins, lipids and nucleic acids in diverse cellular processes. Due to its size and structural simplicity, the transfer of pathogenic or virulent cellular factors across the cells mediated by exosomes is more efficient, hence facilitating the dissemination of viral infections and cancer diseases. The pathogenic role of exosomes in various cancers such as lung and breast, and their potentials as biomarkers have been previously studied, yet limited information is known for Epstein-Barr virus (EBV)-associated cancers. In this chapter, we discuss current evidences that support the pathogenic roles of exosomes in EBV-related cancers and their potentials as biomarkers in cancer diagnostics and therapy response. Here, we also highlight the potential challenges in the development of exosome-based biomarkers for clinical application.

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Hypoxia inducible factor 1α gene (HIF-1α) splice variants: potential prognostic biomarkers in breast cancer

Cited by 47 publications

References 33 publications

Overexpression of hypoxia‐inducible factor 1 alpha impacts FoxP3 levels in mycosis fungoides—Cutaneous T‐cell lymphoma: Clinical implications

Overexpression of hypoxia‐inducible factor 1 alpha impacts FoxP3 levels in mycosis fungoides—Cutaneous T‐cell lymphoma: Clinical implications

Bronchiolitis obliterans after allogeneic hematopoietic SCT: further insight—new perspectives?

Exosomes as the Promising Biomarker for Epstein-Barr Virus (EBV)-Associated Cancers

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