Abstract:
INTRODUCTION:Clinical and pathological characteristics are still considered prognostic markers in metastatic non-small-cell lung cancer (NSCLC) patients but they cannot explain all interindividual variability. Tumoral angiogenesis mediated by the vascular endothelial growth factor (VEGF) is critical for the progression and metastasis of the disease. We aimed to investigate the prognostic role of genetic variants within the VEGF pathway in patients with metastatic NSCLC. MATERIALS AND METHODS:We prospectively included 170 patients with metastatic NSCLC treated with first-line platinum-based chemotherapy. A comprehensive panel of single-nucleotide polymorphisms (SNPs) in genes belonging to the VEGF pathway (VEGFA, VEGFR1/FLT1, VEGFR2/KDR, GRB2, ITGAV, KISS1, KRAS, PRKCE, HIF1α, MAP2K4, MAP2K6, and MAPK11) were genotyped in blood DNA samples. SNPs were evaluated for association with overall survival (OS) and progression-free survival (PFS). RESULTS:In multivariate analyses adjusted for patient characteristics, we found that VEGFA rs2010963 and VEGFR2 rs2071559 were significantly associated with OS [Hazard Ratio (HR) 0.7 (0.5-0.9); p = 0.026 and HR 1.5 (1.1-2.3); p = 0.025, respectively]. Additionally, ITGAV rs35251833 and MAPK11 rs2076139 were significantly associated with PFS [HR 2.5 (1.4-4.3; p = 0.002 and HR 0.6 (0.5-0.9); p = 0.013, respectively]. CONCLUSION:Our findings reinforce the potential clinical value of germline variants in VEGFA and VEGFR2 and show for the first time variants in ITGAV and MAPK11 as promising prognostic markers in metastatic NSCLC patients receiving platinum-based chemotherapy.
journal_name
Angiogenesisjournal_title
Angiogenesisauthors
Sullivan I,Riera P,Andrés M,Altés A,Majem M,Blanco R,Capdevila L,Barba A,Barnadas A,Salazar Jdoi
10.1007/s10456-019-09668-ysubject
Has Abstractpub_date
2019-08-01 00:00:00pages
433-440issue
3eissn
0969-6970issn
1573-7209pii
10.1007/s10456-019-09668-yjournal_volume
22pub_type
杂志文章相关文献
ANGIOGENESIS文献大全abstract:BACKGROUND:Vasculogenic mimicry (VM) is the formation of vascular channels by tumor cells or tumor cell-derived, trans-differentiated cells in highly aggressive, solid tumors. However, the disease features and prognostic value of VM for overall survival of cancer patients remain controversial. METHOD:To systematically...
journal_title:Angiogenesis
pub_type: 杂志文章,meta分析
doi:10.1007/s10456-016-9500-2
更新日期:2016-04-01 00:00:00
abstract::Cancer cells sustain their metabolic needs through nutrients and oxygen supplied by the bloodstream. The requirement for tumor angiogenesis has been therapeutically exploited in the clinical setting mainly by means of inhibition of the vascular endothelial growth factor family of ligands and receptors. Despite promisi...
journal_title:Angiogenesis
pub_type: 临床试验,杂志文章
doi:10.1007/s10456-018-9642-5
更新日期:2019-02-01 00:00:00
abstract::The lymphatic system is intimately linked to tissue fluid homeostasis and immune cell trafficking. These functions are paramount in the establishment and development of an inflammatory response. In the past decade, an increasing number of reports has revealed that marked changes, such as lymphangiogenesis and lymphati...
journal_title:Angiogenesis
pub_type: 杂志文章,评审
doi:10.1007/s10456-014-9416-7
更新日期:2014-04-01 00:00:00
abstract::Among the key effects of fluid shear stress on vascular endothelial cells is modulation of gene expression. Promoter sequences termed shear stress response elements (SSREs) mediate the responsiveness of endothelial genes to shear stress. While previous studies showed that shear stress responsiveness is mediated by a s...
journal_title:Angiogenesis
pub_type: 杂志文章
doi:10.1007/s10456-009-9143-7
更新日期:2009-01-01 00:00:00
abstract::Neovascularization of the inner retinal space is a major cause of vision loss. In retinal angiomatous proliferation (RAP) syndrome, newly formed vessels originate from the retinal plexus and invade the inner retinal space. However, the molecular pathways preventing subretinal vascularization remain largely unknown. In...
journal_title:Angiogenesis
pub_type: 杂志文章
doi:10.1007/s10456-019-09674-0
更新日期:2019-11-01 00:00:00
abstract::Angiogenesis was postulated to be a critical prognostic factor and therapeutic focus for malignancy more than two decades ago. Recent studies indicate quantitative assessments of microvessel count to be an independent prognostic variable for disease-free and overall survival in a wide variety of tumors, and that angio...
journal_title:Angiogenesis
pub_type: 杂志文章
doi:10.1023/A:1018301031580
更新日期:1997-01-01 00:00:00
abstract::The sprouting of endothelial cells is the first step of tumor angiogenesis. Our previous study suggests that miR-153 suppresses breast tumor angiogenesis partially through targeting hypoxia-induced factor (HIF1α). In this study, we demonstrated that miR-153 also suppresses the migration and the tube formation of endot...
journal_title:Angiogenesis
pub_type: 杂志文章
doi:10.1007/s10456-018-9630-9
更新日期:2018-11-01 00:00:00
abstract::Human ribonuclease inhibitor (hRI) can inhibit angiogenesis by reversibly binding angiogenin, a member of the RNaseA superfamily, and by suppressing the expression of basic fibroblast growth factor (bFGF). Angiogenesis is necessary for the growth and metastasis of tumors. To study the links between hRI, angiogenesis, ...
journal_title:Angiogenesis
pub_type: 杂志文章
doi:10.1007/s10456-005-5714-4
更新日期:2005-01-01 00:00:00
abstract::Evidence has been gathered regarding the association between angiogenesis and inflammation in pathological situations. These two phenomena have long been coupled together in many chronic inflammatory disorders with distinct etiopathogenic origin, including psoriasis, rheumatoid arthritis, Crohn's disease, diabetes, an...
journal_title:Angiogenesis
pub_type: 杂志文章,评审
doi:10.1007/s10456-007-9074-0
更新日期:2007-01-01 00:00:00
abstract::Endothelial cells display an extraordinary plasticity both during development and throughout adult life. During early development, endothelial cells assume arterial, venous, or lymphatic identity, while selected endothelial cells undergo additional fate changes to become hematopoietic progenitor, cardiac valve, and ot...
journal_title:Angiogenesis
pub_type: 杂志文章,评审
doi:10.1007/s10456-020-09761-7
更新日期:2021-01-15 00:00:00
abstract::The plasminogen activation system has been implicated in angiogenesis and angiogenesis-dependent diseases such as cancer, atherosclerosis and ocular diseases. The identification and development of inhibitors of angiogenesis offer new possibilities for the treatment of these diseases. To clarify the role of proteins in...
journal_title:Angiogenesis
pub_type: 杂志文章
doi:10.1023/B:AGEN.0000029414.24060.fe
更新日期:2003-01-01 00:00:00
abstract::Ocular angiogenesis is responsible for the majority of irreversible blindness in the developed world [1]. This debilitating complication affects all age groups and characterizes such diverse and widespread diseases as trachoma, retinopathy of prematurity, diabetic retinopathy, neovascular glaucoma and age-related macu...
journal_title:Angiogenesis
pub_type: 杂志文章
doi:10.1023/a:1009071601454
更新日期:1999-01-01 00:00:00
abstract::Endometriosis, defined as the presence of endometrial tissue outside the uterus, is an estrogen-dependent disease which causes pelvic pain and subfertility in women of reproductive age. The condition has a dramatic impact on the professional, social and marital life of sufferers. Direct and indirect evidence suggests ...
journal_title:Angiogenesis
pub_type: 杂志文章,评审
doi:10.1007/s10456-005-9005-x
更新日期:2005-01-01 00:00:00
abstract:BACKGROUND:The term "intramuscular hemangioma capillary type" (IHCT) refers to a fast-flow vascular lesion that is classified as a tumor, although its phenotype overlaps with arteriovenous malformation (AVM). The purpose of this study was to identify somatic mutations in IHCT. METHODS:Affected tissue specimens were ob...
journal_title:Angiogenesis
pub_type: 杂志文章
doi:10.1007/s10456-019-09678-w
更新日期:2019-11-01 00:00:00
abstract::Vascular endothelial (VE) cadherin is a key component of endothelial adherens junctions (AJs) and plays an important role in maintaining vascular integrity. Endocytosis of VE-cadherin regulates junctional strength and a decrease of surface VE-cadherin reduces vascular stability. However, disruption of AJs is also a re...
journal_title:Angiogenesis
pub_type: 杂志文章
doi:10.1007/s10456-018-9638-1
更新日期:2019-02-01 00:00:00
abstract:INTRODUCTION:Endoglin (ENG) forms a receptor complex with ALK1 in endothelial cells (ECs) to promote BMP9/10 signalling. Loss of function mutations in either ENG or ALK1 genes lead to the inherited vascular disorder hereditary haemorrhagic telangiectasia (HHT), characterised by arteriovenous malformations (AVMs). Howev...
journal_title:Angiogenesis
pub_type: 杂志文章
doi:10.1007/s10456-020-09731-z
更新日期:2020-11-01 00:00:00
abstract::Intermittent Hypoxia (IH) that develops in neovascularized solid tumours has been described to positively influence the tumour growth by modulating the behaviour of cancer cells as well as of endothelial cells. However, the molecular mechanisms regulated by IH still remain poorly understood. In this work, the effects ...
journal_title:Angiogenesis
pub_type: 杂志文章
doi:10.1007/s10456-009-9156-2
更新日期:2009-01-01 00:00:00
abstract::During the early stages of angiogenesis, following stimulation of endothelial cells by vascular endothelial growth factor (VEGF), the vascular wall is breached, allowing high molecular weight proteins to leak from the vessels to the interstitial space. This hallmark of angiogenesis results in deposition of a provision...
journal_title:Angiogenesis
pub_type: 杂志文章,评审
doi:10.1007/s10456-010-9170-4
更新日期:2010-06-01 00:00:00
abstract::Pericytes are essential mural cells distinguished by their association with small caliber blood vessels and the presence of a basement membrane shared with endothelial cells. Pericyte interaction with the endothelium plays an important role in angiogenesis; however, very few tools are currently available that allow fo...
journal_title:Angiogenesis
pub_type: 杂志文章
doi:10.1007/s10456-017-9570-9
更新日期:2017-11-01 00:00:00
abstract::Following arterial occlusion, blood vessels respond by forming a new network of functional capillaries (angiogenesis), by reorganizing preexisting capillaries through the recruitment of smooth muscle cells to generate new arteries (arteriogenesis) and by growing and remodeling preexisting collateral arterioles into ph...
journal_title:Angiogenesis
pub_type: 杂志文章,评审
doi:10.1007/s10456-016-9535-4
更新日期:2017-02-01 00:00:00
abstract::Inhibiting pathologic angiogenesis can halt disease progression, but such inhibition may offer only a temporary benefit, followed by tissue revascularization after treatment stoppage. This revascularization, however, occurs by largely unknown phenotypic changes in pathologic vessels. To investigate the dynamics of ves...
journal_title:Angiogenesis
pub_type: 杂志文章
doi:10.1007/s10456-019-09679-9
更新日期:2019-11-01 00:00:00
abstract::The formation of new tubular structures from a quiescent endothelial lining is one of the hallmarks of sprouting angiogenesis. This process can be mimicked in vitro by inducing capillary-like tubular structures in a three-dimensional (3D) fibrin matrix. We aimed to analyze the differential mRNA expression in two pheno...
journal_title:Angiogenesis
pub_type: 杂志文章
doi:10.1007/s10456-007-9086-9
更新日期:2008-01-01 00:00:00
abstract::Therapeutic angiogenesis is a promising strategy to promote the formation of new or collateral vessels for tissue regeneration and repair. Since changes in tissue oxygen concentrations are known to stimulate numerous cell functions, these studies have focused on the oxygen microenvironment and its role on the angiogen...
journal_title:Angiogenesis
pub_type: 杂志文章
doi:10.1007/s10456-009-9152-6
更新日期:2009-01-01 00:00:00
abstract::Therapeutic over-expression of vascular endothelial growth factor (VEGF) can be used to treat ischemic conditions. However, VEGF can induce either normal or aberrant angiogenesis depending on its dose in the microenvironment around each producing cell in vivo, which limits its clinical usefulness. The goal herein was ...
journal_title:Angiogenesis
pub_type: 杂志文章
doi:10.1007/s10456-012-9304-y
更新日期:2013-01-01 00:00:00
abstract::Anti-VEGF (vascular endothelial growth factor) therapy with the monoclonal antibody bevacizumab can cause gastrointestinal (GI) perforations. In recent years it became apparent that GI perforations also occur during treatment with antiangiogenic tyrosine kinase inhibitors (TKIs). It is of clinical importance to consid...
journal_title:Angiogenesis
pub_type: 杂志文章,评审
doi:10.1007/s10456-010-9197-6
更新日期:2011-05-01 00:00:00
abstract::The hst-1 gene product, one of the fibroblast growth factor family proteins, has transforming and angiogenic activities. The BALB/c 3T3 cell line was transfected with an expression vector harboring human hst-1 cDNA and the malignant properties of two stably transfected clones, TC-1 and TC-2, were examined. The stimula...
journal_title:Angiogenesis
pub_type: 杂志文章
doi:10.1023/a:1009288405970
更新日期:1998-01-01 00:00:00
abstract:BACKGROUND:EPLIN (epithelial protein lost in neoplasm) is a cytoskeletal associated protein involved in the regulation of actin dynamics and subsequently in cell motility. EPLIN expression is frequently reduced in a variety of cancer cells and tissues and this loss may account for increased invasive traits in cancer ce...
journal_title:Angiogenesis
pub_type: 杂志文章
doi:10.1007/s10456-010-9188-7
更新日期:2010-12-01 00:00:00
abstract::Although monotherapy with angiostatic drugs is still far from effective, there is abundant evidence that angiostatic therapy can improve the efficacy of conventional treatments like radiotherapy. This has instigated numerous efforts to optimize and clinically implement the combination of angiostatic drugs with radiati...
journal_title:Angiogenesis
pub_type: 历史文章,杂志文章,评审
doi:10.1007/s10456-017-9546-9
更新日期:2017-05-01 00:00:00
abstract::Vascularization and endothelial phenotype were investigated in embryonic tissues grafted onto chorioallantoic membrane (CAM) by means of immunocytochemistry and electron microscopy. Single grafts of adrenal gland or cerebellum and double grafts of adrenal gland plus cerebellum were performed, using tissues from chick ...
journal_title:Angiogenesis
pub_type: 杂志文章
doi:10.1023/a:1026550510585
更新日期:1999-01-01 00:00:00
abstract::Rheumatoid arthritis (RA) is a chronic destructive musculo-skeletal disorder, associated with thickening of the synovial membrane lining the joints, inflammation and hyperproliferation of synovial cells, as well as a pro-inflammatory cytokine cascade, leukocyte infiltration, and tissue damage and bone resorption. An e...
journal_title:Angiogenesis
pub_type: 杂志文章
doi:10.1023/a:1009229508096
更新日期:1998-01-01 00:00:00