Abstract:
:The current management of colorectal cancer (CRC) would greatly benefit from non-invasive prognostic biomarkers indicative of clinicopathological tumor characteristics. Here, we employed targeted proteomic profiling of 80 glycoprotein biomarker candidates across plasma samples of a well-annotated patient cohort with comprehensive CRC characteristics. Clinical data included 8-year overall survival, tumor staging, histological grading, regional localization, and molecular tumor characteristics. The acquired quantitative proteomic dataset was subjected to the development of biomarker signatures predicting prognostic clinical endpoints. Protein candidates were selected into the signatures based on significance testing and a stepwise protein selection, each within 10-fold cross-validation. A six-protein biomarker signature of patient outcome could predict survival beyond clinical stage and was able to stratify patients into groups of better and worse prognosis. We further evaluated the performance of the signature on the mRNA level and assessed its prognostic value in the context of previously published transcriptional signatures. Additional signatures predicting regional tumor localization and disease dissemination were also identified. The integration of rich clinical data, quantitative proteomic technologies, and tailored computational modeling facilitated the characterization of these signatures in patient circulation. These findings highlight the value of a simultaneous assessment of important prognostic disease characteristics within a single measurement.
journal_name
EMBO Mol Medjournal_title
EMBO molecular medicineauthors
Surinova S,Radová L,Choi M,Srovnal J,Brenner H,Vitek O,Hajdúch M,Aebersold Rdoi
10.15252/emmm.201404874subject
Has Abstractpub_date
2015-09-01 00:00:00pages
1153-65issue
9eissn
1757-4676issn
1757-4684pii
emmm.201404874journal_volume
7pub_type
杂志文章abstract::While increased VEGF-A has been associated with neovascular age-related macular degeneration (AMD), it is not known whether VEGF-A may also promote other age-related eye diseases. Here, we show that an increase in VEGF-A is sufficient to cause multiple distinct common aging diseases of the eye, including cataracts and...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.15252/emmm.201505613
更新日期:2016-03-01 00:00:00
abstract::Patients affected by mitochondrial OXPHOS disorders are still faced with a grim lack of therapeutic options. In this Closeup, Carlos Moraes revisits the recent data by Giovanni Manfredi on PKA's functions in the mitochondria and now its modulation can improve respiration and ATP production in COX-defective cells. ...
journal_title:EMBO molecular medicine
pub_type: 评论,杂志文章
doi:10.1002/emmm.200900049
更新日期:2009-11-01 00:00:00
abstract::Glycine transporters (GlyT1 and GlyT2) that regulate levels of brain glycine, an inhibitory neurotransmitter with co-agonist activity for NMDA receptors (NMDARs), have been considered to be important targets for the treatment of brain disorders with suppressed NMDAR function such as schizophrenia. However, it remains ...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.15252/emmm.202012632
更新日期:2021-01-11 00:00:00
abstract::Arteriogenesis-the growth of collateral arterioles-partially compensates for the progressive occlusion of large conductance arteries as it may occur as a consequence of coronary, cerebral or peripheral artery disease. Despite being clinically highly relevant, mechanisms driving this process remain elusive. In this con...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.15252/emmm.201403864
更新日期:2014-08-01 00:00:00
abstract::Dilated cardiomyopathy (DCM) is a life-threatening disorder whose genetic basis is heterogeneous and mostly unknown. Five Arab Christian infants, aged 4-30 months from four families, were diagnosed with DCM associated with mild skin, teeth, and hair abnormalities. All passed away before age 3. A homozygous sequence va...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.15252/emmm.201606523
更新日期:2017-03-01 00:00:00
abstract::Telomerase is expressed in the neonatal brain, in distinct regions of adult brain, and was shown to protect developing neurons from apoptosis. Telomerase reactivation by gene manipulation reverses neurodegeneration in aged telomerase-deficient mice. Hence, we and others hypothesized that increasing telomerase expressi...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.1002/emmm.201200212
更新日期:2012-04-01 00:00:00
abstract::Maladaptive plasticity involving increased expression of AMPA-type glutamate receptors is involved in several pathologies, including neuropathic pain, but direct inhibition of AMPARs is associated with side effects. As an alternative, we developed a cell-permeable, high-affinity (~2 nM) peptide inhibitor, Tat-P4 -(C5)...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.15252/emmm.201911248
更新日期:2020-06-08 00:00:00
abstract::Aging is associated with redox imbalance according to the redox theory of aging. Consistently, a mouse model of premature aging (LmnaG609G/+ ) showed an increased level of mitochondrial reactive oxygen species (ROS) and a reduced basal antioxidant capacity, including loss of the NADPH-coupled glutathione redox system....
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.15252/emmm.202012423
更新日期:2020-10-07 00:00:00
abstract::Transferring large or multiple genes into primary human stem/progenitor cells is challenged by restrictions in vector capacity, and this hurdle limits the success of gene therapy. A paradigm is Duchenne muscular dystrophy (DMD), an incurable disorder caused by mutations in the largest human gene: dystrophin. The combi...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.15252/emmm.201607284
更新日期:2018-02-01 00:00:00
abstract::Diabetic nephropathy is the leading cause of end-stage renal disease. Although dysfunction of podocytes, also termed glomerular visceral epithelial cells, is critically associated with diabetic nephropathy, the mechanism underlying podocyte dysfunction still remains obscure. Here, we identify that KDM6A, a histone lys...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.15252/emmm.201809828
更新日期:2019-05-01 00:00:00
abstract::Familial Mediterranean fever (FMF) is the most frequent hereditary systemic autoinflammatory syndrome. FMF is usually caused by biallelic mutations in the MEFV gene, encoding Pyrin. Conclusive genetic evidence lacks for about 30% of patients diagnosed with clinical FMF. Pyrin is an inflammasome sensor maintained inact...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.15252/emmm.201910547
更新日期:2019-11-07 00:00:00
abstract::Autologous haematopoietic stem cell transplantation is highly efficient for the treatment of systemic autoimmune diseases, but its consequences for the immune system remain poorly understood. Here, we describe an optimized RNA-based technology for unbiased amplification of T cell receptor beta-chain libraries and use ...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.1002/emmm.201100129
更新日期:2011-04-01 00:00:00
abstract::The zinc transporter protein ZIP13 plays critical roles in bone, tooth, and connective tissue development, and its dysfunction is responsible for the spondylocheirodysplastic form of Ehlers-Danlos syndrome (SCD-EDS, OMIM 612350). Here, we report the molecular pathogenic mechanism of SCD-EDS caused by two different mut...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.15252/emmm.201303809
更新日期:2014-08-01 00:00:00
abstract::Breast cancer is a molecularly, biologically and clinically heterogeneous group of disorders. Understanding this diversity is essential to improving diagnosis and optimizing treatment. Both genetic and acquired epigenetic abnormalities participate in cancer, but the involvement of the epigenome in breast cancer and it...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.1002/emmm.201100801
更新日期:2011-12-01 00:00:00
abstract::Mammary epithelial stem cells are fundamental to maintain tissue integrity. Cancer stem cells (CSCs) are implicated in both treatment resistance and disease relapse, and the molecular bases of their malignant properties are still poorly understood. Here we show that both normal stem cells and CSCs of the breast are co...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.1002/emmm.201302909
更新日期:2014-01-01 00:00:00
abstract::Clinical application of lentiviral vector (LV)-based hematopoietic stem and progenitor cells (HSPC) gene therapy is rapidly becoming a reality. Nevertheless, LV-mediated signaling and its potential functional consequences on HSPC biology remain poorly understood. We unravel here a remarkably limited impact of LV on th...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.15252/emmm.201707922
更新日期:2017-09-01 00:00:00
abstract::Lysosomal storage diseases (LSDs) are a group of genetic disorders due to defects in any aspect of lysosomal biology. During the past two decades, different approaches have been introduced for the treatment of these conditions. Among them, enzyme replacement therapy (ERT) represented a major advance and is used succes...
journal_title:EMBO molecular medicine
pub_type: 杂志文章,评审
doi:10.1002/emmm.200900036
更新日期:2009-08-01 00:00:00
abstract::The cell fate determinant Numb is frequently downregulated in human breast cancers (BCs), resulting in p53 inactivation and an aggressive disease course. In the mouse mammary gland, Numb/p53 downregulation leads to aberrant tissue morphogenesis, expansion of the stem cell compartment, and emergence of cancer stem cell...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.15252/emmm.201606940
更新日期:2017-05-01 00:00:00
abstract::Systemic toxicities have severely limited the clinical application of tumor necrosis factor (TNF) as an anticancer agent. Activity-on-Target cytokines (AcTakines) are a novel class of immunocytokines with improved therapeutic index. A TNF-based AcTakine targeted to CD13 enables selective activation of the tumor neovas...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.15252/emmm.201911223
更新日期:2020-02-07 00:00:00
abstract::There is a widespread agreement from patient and professional organisations alike that the safety of stem cell therapeutics is of paramount importance, particularly for ex vivo autologous gene therapy. Yet current technology makes it difficult to thoroughly evaluate the behaviour of genetically corrected stem cells be...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.15252/emmm.201404353
更新日期:2015-04-01 00:00:00
abstract::Fibroblast growth factors (FGFs) play key roles in the pathogenesis of different human diseases, but the cross-talk between FGFs and other cytokines remains largely unexplored. We identified an unexpected antagonistic effect of FGFs on the interferon (IFN) signaling pathway. Genetic or pharmacological inhibition of FG...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.15252/emmm.201911793
更新日期:2020-09-07 00:00:00
abstract::Formation of pathogenic antibodies is a major problem in replacement therapies for inherited protein deficiencies. For example, antibodies to coagulation factors ('inhibitors') seriously complicate treatment of haemophilia. While immune tolerance induction (ITI) protocols have been developed, inhibitors against factor...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.1002/emmm.201302859
更新日期:2013-11-01 00:00:00
abstract::Synaptic inhibition is essential for shaping the dynamics of neuronal networks, and aberrant inhibition plays an important role in neurological disorders. Gephyrin is a central player at inhibitory postsynapses, directly binds and organizes GABAA and glycine receptors (GABAARs and GlyRs), and is thereby indispensable ...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.15252/emmm.201505323
更新日期:2015-12-01 00:00:00
abstract::Mutations in POLG disrupt mtDNA replication and cause devastating diseases often with neurological phenotypes. Defining disease mechanisms has been hampered by limited access to human tissues, particularly neurons. Using patient cells carrying POLG mutations, we generated iPSCs and then neural stem cells. These neural...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.15252/emmm.202012146
更新日期:2020-10-07 00:00:00
abstract::Candida albicans is a frequent aetiologic agent of sepsis associated with high mortality in immunocompromised patients. Developing new antifungal therapies is a medical need due to the low efficiency and resistance to current antifungal drugs. Here, we show that p38γ and p38δ regulate the innate immune response to C. ...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.15252/emmm.201708485
更新日期:2018-05-01 00:00:00
abstract::Although remnant cardiomyocytes (CMs) possess a certain degree of proliferative ability, efficiency is too low for cardiac regeneration after injury. In this study, we identified a distinct stage within the initiation phase of CM reprogramming before the MET process, and microarray analysis revealed the strong up-regu...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.15252/emmm.201606558
更新日期:2017-02-01 00:00:00
abstract::The combinations of genetic alterations that cooperate with von Hippel-Lindau (VHL) mutation to cause clear cell renal cell carcinoma (ccRCC) remain poorly understood. We show that the TP53 tumour suppressor gene is mutated in approximately 9% of human ccRCCs. Combined deletion of Vhl and Trp53 in primary mouse embryo...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.1002/emmm.201202231
更新日期:2013-06-01 00:00:00
abstract::Disease modeling with induced pluripotent stem cells (iPSCs) is creating an abundance of phenotypic information that has become difficult to follow and interpret. Here, we report a systematic analysis of research practices and reporting bias in neurological disease models from 93 published articles. We find heterogene...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.15252/emmm.201708191
更新日期:2017-12-01 00:00:00
abstract::The serotonin 2C receptor regulates food uptake, and its activity is regulated by alternative pre-mRNA splicing. Alternative exon skipping is predicted to generate a truncated receptor protein isoform, whose existence was confirmed with a new antiserum. The truncated receptor sequesters the full-length receptor in int...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.15252/emmm.201506030
更新日期:2016-08-01 00:00:00
abstract::KCNN3, encoding the small conductance calcium-activated potassium channel SK3, harbours a polymorphic CAG repeat in the amino-terminal coding region with yet unproven function. Hypothesizing that KCNN3 genotypes do not influence susceptibility to schizophrenia but modify its phenotype, we explored their contribution t...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.1002/emmm.201100135
更新日期:2011-06-01 00:00:00