Abstract:
BACKGROUND:Molecular subtyping of cancer aimed to predict patient overall survival (OS) and nominate drug targets for patient treatments is central to precision oncology. Owing to the rapid development of phosphoproteomics, we can now measure thousands of phosphoproteins in human cancer tissues. However, limited studies report how to analyse the complex phosphoproteomic data for cancer subtyping and to nominate druggable kinase candidates. FINDINGS:In this work, we reanalysed the phosphoproteomic data of high-grade serous ovarian cancer (HGSOC) from the Clinical Proteomic Tumour Analysis Consortium (CPTAC). Our analysis classified HGSOC into 5 major subtypes that were associated with different OS and appeared to be more accurate than that achieved with protein profiling. We provided a workflow to identify 29 kinases whose increased activities in tumours are associated with poor survival. The altered kinase signalling landscape of HGSOC included the PI3K/AKT/mTOR, cell cycle and MAP kinase signalling pathways. We also developed a "patient-specific" hierarchy of clinically actionable kinases and selected kinase inhibitors by considering kinase activation and kinase inhibitor selectivity. INTERPRETATION:Our study offered a global phosphoproteomics data analysis workflow to aid in cancer molecular subtyping, determining phosphorylation-based cancer hallmarks and facilitating nomination of kinase inhibition in cancer.
journal_name
EBioMedicinejournal_title
EBioMedicineauthors
Tong M,Yu C,Zhan D,Zhang M,Zhen B,Zhu W,Wang Y,Wu C,He F,Qin J,Li Tdoi
10.1016/j.ebiom.2018.12.039subject
Has Abstractpub_date
2019-02-01 00:00:00pages
305-317issn
2352-3964pii
S2352-3964(18)30616-9journal_volume
40pub_type
杂志文章相关文献
EBioMedicine文献大全abstract::Clear cell renal cell carcinoma (ccRCC) is the most lethal neoplasm of the urologic system. Clinical therapeutic effect varies greatly between individual ccRCC patients, so there is an urgent need to develop prognostic molecular biomarkers to help clinicians identify patients in need of early aggressive management. In...
journal_title:EBioMedicine
pub_type: 杂志文章
doi:10.1016/j.ebiom.2016.12.003
更新日期:2017-02-01 00:00:00
abstract:BACKGROUND:Colistin resistance mediated by mcr-1-harbouring plasmids is an emerging threat in Enterobacteriaceae, like Salmonella. Based on its major contribution to the diarrhoea burden, the epidemic state and threat of mcr-1-harbouring Salmonella in community-acquired infections should be estimated. METHODS:This ret...
journal_title:EBioMedicine
pub_type: 历史文章,杂志文章
doi:10.1016/j.ebiom.2019.03.006
更新日期:2019-04-01 00:00:00
abstract:BACKGROUND:Glioblastoma (GBM), a highly malignant brain tumor, invariably recurs after therapy. Quiescent GBM cells represent a potential source of tumor recurrence, but little is known about their molecular underpinnings. METHODS:Patient-derived GBM cells were engineered by CRISPR/Cas9-assisted knock-in of an inducib...
journal_title:EBioMedicine
pub_type: 杂志文章
doi:10.1016/j.ebiom.2019.03.064
更新日期:2019-04-01 00:00:00
abstract:BACKGROUND:Recurrent implantation failure (RIF) remains a critical and challenging problem in assisted reproductive technology mainly due to impaired decidualization. The endocytic and transcytotic activity in the endometrium are crucial for decidualization. The most representative endocytic gene is the C-terminal Eps1...
journal_title:EBioMedicine
pub_type: 杂志文章
doi:10.1016/j.ebiom.2019.10.018
更新日期:2019-12-01 00:00:00
abstract:BACKGROUND:Angiogenesis improves reperfusion to the ischaemic tissue after vascular obstruction. The underlying molecular mechanisms of post-ischaemic angiogenesis are not clear. FAM3A belongs to the family with sequence similarity 3 (FAM3) genes, but its biological function in endothelial cells in regards to vascular ...
journal_title:EBioMedicine
pub_type: 杂志文章
doi:10.1016/j.ebiom.2019.03.038
更新日期:2019-05-01 00:00:00
abstract:BACKGROUND:Pediatric high-grade gliomas (pHGG) are the leading cause of cancer-related death during childhood. Due to their diffuse growth characteristics, chemoresistance and location behind the blood-brain barrier (BBB), the prognosis of pHGG has barely improved in the past decades. As such, there is a dire need for ...
journal_title:EBioMedicine
pub_type: 杂志文章
doi:10.1016/j.ebiom.2019.10.062
更新日期:2019-12-01 00:00:00
abstract::Nonalcoholic fatty liver disease is a highly prevalent component of disorders associated with disrupted energy homeostasis. Although dysregulation of the energy sensor AMP-activated protein kinase (AMPK) is viewed as a pathogenic factor in the development of fatty liver its role has not been directly demonstrated. Une...
journal_title:EBioMedicine
pub_type: 杂志文章
doi:10.1016/j.ebiom.2018.01.008
更新日期:2018-02-01 00:00:00
abstract::Individual differences in susceptibility to human immunodeficiency virus type 1 (HIV-1) infection have been of interest for decades. We aimed to determine the contribution of large isoform of Mammalian DnaJ (MRJ-L), a HIV-1 Vpr-interacting cellular protein, to this natural variation. Expression of MRJ-L in monocyte-de...
journal_title:EBioMedicine
pub_type: 杂志文章
doi:10.1016/j.ebiom.2014.10.002
更新日期:2014-10-07 00:00:00
abstract:BACKGROUND:There is currently no anti-fibrotic drug therapy available to treat hepatitis C virus (HCV) cirrhosis. The aim of this study was to assess the safety, tolerability, and anti-fibrotic effect of PRI-724, a small-molecule modulator of Wnt signaling, in patients with HCV cirrhosis. METHODS:In this single-center...
journal_title:EBioMedicine
pub_type: 杂志文章
doi:10.1016/j.ebiom.2017.08.016
更新日期:2017-09-01 00:00:00
abstract:BACKGROUND:We developed and validated an integrated radiomic-clinicopathologic nomogram (RadClip) for post-surgical biochemical recurrence free survival (bRFS) and adverse pathology (AP) prediction in men with prostate cancer (PCa). RadClip was further compared against extant prognostics tools like CAPRA and Decipher. ...
journal_title:EBioMedicine
pub_type: 杂志文章
doi:10.1016/j.ebiom.2020.103163
更新日期:2021-01-01 00:00:00
abstract::Glycated haemoglobin (HbA1c) is the most important marker of hyperglycaemia in diabetes mellitus. We show that d-ribose reacts with haemoglobin, thus yielding HbA1c. Using mass spectrometry, we detected glycation of haemoglobin with d-ribose produces 10 carboxylmethyllysines (CMLs). The first-order rate constant of fr...
journal_title:EBioMedicine
pub_type: 杂志文章
doi:10.1016/j.ebiom.2017.10.001
更新日期:2017-11-01 00:00:00
abstract:BACKGROUND:A tick-borne segmented RNA virus called Jingmen tick virus (JMTV) was recently identified, variants of which were detected in a non-human primate host and fatal patients with Crimean-Congo haemorrhagic fever. We investigated its infectivity and pathogenicity for humans. METHODS:We obtained skin-biopsy, bloo...
journal_title:EBioMedicine
pub_type: 杂志文章
doi:10.1016/j.ebiom.2019.04.004
更新日期:2019-05-01 00:00:00
abstract:BACKGROUND:Recurrent mutations in the promoter of the telomerase reverse transcriptase (TERT) gene (C228T and C250T) detected in tumours and cells shed into urine of urothelial cancer (UC) patients are putative biomarkers for UC detection and monitoring. However, the possibility of detecting these mutations in cell-fre...
journal_title:EBioMedicine
pub_type: 杂志文章
doi:10.1016/j.ebiom.2019.05.004
更新日期:2019-06-01 00:00:00
abstract:BACKGROUND:Epidemiological, laboratory and clinical studies have established an association between elevated urate and high blood pressure (BP). However, the inference of causality remains controversial. A naturally occurring antioxidant, urate may also be neuroprotective, and urate-elevating treatment with its precurs...
journal_title:EBioMedicine
pub_type: 杂志文章,随机对照试验
doi:10.1016/j.ebiom.2018.10.039
更新日期:2018-11-01 00:00:00
abstract:BACKGROUND:Visual function and brain function decline concurrently with aging. Notably, cataract patients often present with accelerated age-related decreases in brain function, but the underlying mechanisms are still unclear. Optical structures of the anterior segment of the eyes, such as the lens and cornea, can be r...
journal_title:EBioMedicine
pub_type: 杂志文章
doi:10.1016/j.ebiom.2018.03.002
更新日期:2018-04-01 00:00:00
abstract::Autophagy is a catabolic process that facilitates nutrient recycling via degradation of damaged organelles and proteins through lysosomal mediated degradation. Alterations in this complex, and tightly regulated process, lead to disease. Autophagy is widely accepted as cytoprotective against neurodegenerative diseases ...
journal_title:EBioMedicine
pub_type: 杂志文章,评审
doi:10.1016/j.ebiom.2016.10.034
更新日期:2016-12-01 00:00:00
abstract::Intestinal damage in malnutrition constitutes a threat to the survival of many thousands of children globally. We studied children in Lusaka, Zambia, with severe acute malnutrition (SAM) and persistent diarrhea using endoscopy, biopsy and analysis of markers and protective proteins in blood and intestinal secretions. ...
journal_title:EBioMedicine
pub_type: 杂志文章
doi:10.1016/j.ebiom.2017.07.017
更新日期:2017-08-01 00:00:00
abstract:BACKGROUND:Pleural fibrosis is defined as excessive depositions of matrix components that result in pleural tissue architecture destruction and dysfunction. In severe cases, the progression of pleural fibrosis leads to lung entrapment, resulting in dyspnea and respiratory failure. However, the mechanism of pleural fibr...
journal_title:EBioMedicine
pub_type: 杂志文章
doi:10.1016/j.ebiom.2019.02.057
更新日期:2019-03-01 00:00:00
abstract:BACKGROUND:Some interstitial lung disease (ILD) patients develop a progressive fibrosing-ILD phenotype (PF-ILD), with similar persistent lung function decline suggesting common molecular pathways involved. Nintedanib, a tyrosine kinase inhibitor targeting the PDGF, FGF, VEGF and M-CSF pathways, has shown comparable eff...
journal_title:EBioMedicine
pub_type: 杂志文章
doi:10.1016/j.ebiom.2019.10.050
更新日期:2019-12-01 00:00:00
abstract:BACKGROUND:Corneal neovascularization (angiogenesis and lymphangiogenesis) compromises corneal transparency and transplant survival, however, the molecular mechanisms of corneal host epithelial and stromal cells in neovascularization have not yet been fully elucidated. Furthermore, the contribution and mechanism of cor...
journal_title:EBioMedicine
pub_type: 杂志文章
doi:10.1016/j.ebiom.2019.05.026
更新日期:2019-06-01 00:00:00
abstract::Pericardial tuberculosis (TB) is associated with high therapy failure and high mortality rates. Antibiotics have to penetrate to site of infection at sufficient non-protein bound concentrations, and then enter bacteria to inhibit intracellular biochemical processes. The antibiotic concentrations achieved in pericardia...
journal_title:EBioMedicine
pub_type: 杂志文章
doi:10.1016/j.ebiom.2015.09.025
更新日期:2015-09-16 00:00:00
abstract:BACKGROUND:Preoperative prediction of lymph node (LN) status is of crucial importance for appropriate treatment planning in patients with colorectal cancer (CRC). In this study, we sought to develop and validate a non-invasive nomogram model to preoperatively predict LN metastasis in CRC. METHODS:Development of the no...
journal_title:EBioMedicine
pub_type: 杂志文章
doi:10.1016/j.ebiom.2018.09.052
更新日期:2018-11-01 00:00:00
abstract:BACKGROUND:Abdominal fat mass is associated with metabolic risk whilst gluteal femoral fat is paradoxically protective. MicroRNAs are known to be necessary for adipose tissue formation and function but their role in regulating human fat distribution remains largely unexplored. METHODS:An initial microarray screen of a...
journal_title:EBioMedicine
pub_type: 杂志文章
doi:10.1016/j.ebiom.2019.05.047
更新日期:2019-06-01 00:00:00
abstract:BACKGROUND:While PARP inhibitors and CDK4/6 inhibitors, the two classes of FDA-approved agents, have shown promising clinical benefits, there is an urgent need to develop new therapeutic strategies to improve clinical response. Meanwhile, extending the utility of these inhibitors beyond their respective molecularly def...
journal_title:EBioMedicine
pub_type: 杂志文章
doi:10.1016/j.ebiom.2019.03.027
更新日期:2019-05-01 00:00:00
abstract:BACKGROUND:The delineation of the behavioral neurobiological mechanisms underlying the heterogeneous pathways for alcohol use disorders (AUDs) is ostensibly imperative for the development of more cost-effective treatments predicated on better understanding of this complex psychopathology. METHODS:1) Forty-eight high a...
journal_title:EBioMedicine
pub_type: 杂志文章
doi:10.1016/j.ebiom.2017.11.025
更新日期:2018-01-01 00:00:00
abstract::Pancreatic ductal adenocarcinoma (PDAC) shows remarkable propensity to metastasize. This predilection to escape from the primary tumor is driven by paracrine and autocrine mechanisms that guide cancer cells through a multi-step process concluding with colonization in distant tissues. Although cell-intrinsic features s...
journal_title:EBioMedicine
pub_type: 杂志文章,评审
doi:10.1016/j.ebiom.2020.102662
更新日期:2020-03-01 00:00:00
abstract:BACKGROUND:Impaired fracture healing represents an ongoing clinical challenge, as treatment options remain limited. Calcitonin gene-related peptide (CGRP), a neuropeptide targeted by emerging anti-migraine drugs, is also expressed in sensory nerve fibres innervating bone tissue. METHOD:Bone healing following a femoral...
journal_title:EBioMedicine
pub_type: 杂志文章
doi:10.1016/j.ebiom.2020.102970
更新日期:2020-09-01 00:00:00
abstract::Environmental exposure early in development plays a role in susceptibility to disease in later life. Here, we demonstrate that prolonged febrile seizures induced by exposure of rat pups to a hyperthermic environment enhance seizure susceptibility not only in these hyperthermia-treated rats but also in their future off...
journal_title:EBioMedicine
pub_type: 杂志文章
doi:10.1016/j.ebiom.2017.02.006
更新日期:2017-03-01 00:00:00
abstract:BACKGROUND:Interpretation of the increase in certain inflammatory markers in virally suppressed HIV-infected individuals must rely on an appropriate uninfected control group well characterized for non-HIV-related factors that contribute to chronic inflammation, e.g. smoking, alcohol consumption, or being overweight. We...
journal_title:EBioMedicine
pub_type: 杂志文章
doi:10.1016/j.ebiom.2020.103129
更新日期:2020-12-01 00:00:00
abstract:BACKGROUND:Intervertebral disc degeneration (IDD) is a major contributor to lower back pain, however, the molecular and pathogenetic mechanisms underlying IDD are poorly understood. As a high-risk factor for IDD, compression stress was reported to induce apoptosis of nucleus pulposus (NP) cells and extracellular matrix...
journal_title:EBioMedicine
pub_type: 杂志文章
doi:10.1016/j.ebiom.2020.102679
更新日期:2020-03-01 00:00:00