Molecular subtyping of cancer and nomination of kinase candidates for inhibition with phosphoproteomics: Reanalysis of CPTAC ovarian cancer.


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.






Tong M,Yu C,Zhan D,Zhang M,Zhen B,Zhu W,Wang Y,Wu C,He F,Qin J,Li T




Has Abstract


2019-02-01 00:00:00










  • Galactosylation and Sialylation Levels of IgG Predict Relapse in Patients With PR3-ANCA Associated Vasculitis.

    abstract:OBJECTIVE:The objective of our study is to investigate the Fc glycosylation profiles of both antigen-specific IgG targeted against proteinase 3 (PR3-ANCA) and total IgG as prognostic markers of relapse in patients with Granulomatosis with Polyangiitis (GPA). METHODS:Seventy-five patients with GPA and a PR3-ANCA rise d...


    pub_type: 杂志文章


    authors: Kemna MJ,Plomp R,van Paassen P,Koeleman CAM,Jansen BC,Damoiseaux JGMC,Cohen Tervaert JW,Wuhrer M

    更新日期:2017-03-01 00:00:00

  • Building the Evidence Base of Blood-Based Biomarkers for Early Detection of Cancer: A Rapid Systematic Mapping Review.

    abstract:BACKGROUND:The Early Cancer Detection Consortium is developing a blood-test to screen the general population for early identification of cancer, and has therefore conducted a systematic mapping review to identify blood-based biomarkers that could be used for early identification of cancer. METHODS:A mapping review wit...


    pub_type: 杂志文章,meta分析,评审


    authors: Uttley L,Whiteman BL,Woods HB,Harnan S,Philips ST,Cree IA,Early Cancer Detection Consortium.

    更新日期:2016-08-01 00:00:00

  • Exosome Derived From Human Umbilical Cord Mesenchymal Stem Cell Mediates MiR-181c Attenuating Burn-induced Excessive Inflammation.

    abstract::Mesenchymal stem cell (MSC)-derived exosomes have diverse functions in regulating wound healing and inflammation; however, the molecular mechanism of human umbilical cord MSC (hUCMSC)-derived exosomes in regulating burn-induced inflammation is not well understood. We found that burn injury significantly increased the ...


    pub_type: 杂志文章


    authors: Li X,Liu L,Yang J,Yu Y,Chai J,Wang L,Ma L,Yin H

    更新日期:2016-06-01 00:00:00

  • d-Ribose as a Contributor to Glycated Haemoglobin.

    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...


    pub_type: 杂志文章


    authors: Chen X,Su T,Chen Y,He Y,Liu Y,Xu Y,Wei Y,Li J,He R

    更新日期:2017-11-01 00:00:00

  • Plasma Circulating Extracellular RNAs in Left Ventricular Remodeling Post-Myocardial Infarction.

    abstract::Despite substantial declines in mortality following myocardial infarction (MI), subsequent left ventricular remodeling (LVRm) remains a significant long-term complication. Extracellular small non-coding RNAs (exRNAs) have been associated with cardiac inflammation and fibrosis and we hypothesized that they are associat...


    pub_type: 杂志文章,随机对照试验


    authors: Danielson KM,Shah R,Yeri A,Liu X,Camacho Garcia F,Silverman M,Tanriverdi K,Das A,Xiao C,Jerosch-Herold M,Heydari B,Abbasi S,Van Keuren-Jensen K,Freedman JE,Wang YE,Rosenzweig A,Kwong RY,Das S

    更新日期:2018-06-01 00:00:00

  • Identification of Associations Between Prescribed Medications and Cancer: A Nationwide Screening Study.

    abstract:PURPOSE:We present a systematic screening for identifying associations between prescribed drugs and cancer risk using the high quality Danish nationwide health registries. METHODS:We identified all patients (cases) with incident cancer in Denmark during 2000-2012 (n=278,485) and matched each case to 10 controls. Compl...


    pub_type: 杂志文章


    authors: Pottegård A,Friis S,Christensen Rd,Habel LA,Gagne JJ,Hallas J

    更新日期:2016-05-01 00:00:00

  • Recapitulation of hepatitis B virus-host interactions in liver organoids from human induced pluripotent stem cells.

    abstract::Therapies against hepatitis B virus (HBV) have improved in recent decades; however, the development of individualized treatments has been limited by the lack of individualized infection models. In this study, we used human induced pluripotent stem cell (hiPSC) to generate a functional liver organoid (LO) that inherite...


    pub_type: 杂志文章


    authors: Nie YZ,Zheng YW,Miyakawa K,Murata S,Zhang RR,Sekine K,Ueno Y,Takebe T,Wakita T,Ryo A,Taniguchi H

    更新日期:2018-09-01 00:00:00

  • Tissue Microbiome Profiling Identifies an Enrichment of Specific Enteric Bacteria in Opisthorchis viverrini Associated Cholangiocarcinoma.

    abstract::Cholangiocarcinoma (CCA) is the primary cancer of the bile duct system. The role of bile duct tissue microbiomes in CCA tumorigenesis is unestablished. To address this, sixty primary CCA tumors and matched normals, from both liver fluke (Opisthorchis viverrini) associated (OVa, n=28) and non-O. viverrini associated (n...


    pub_type: 杂志文章


    authors: Chng KR,Chan SH,Ng AHQ,Li C,Jusakul A,Bertrand D,Wilm A,Choo SP,Tan DMY,Lim KH,Soetinko R,Ong CK,Duda DG,Dima S,Popescu I,Wongkham C,Feng Z,Yeoh KG,Teh BT,Yongvanit P,Wongkham S,Bhudhisawasdi V,Khuntikeo N,T

    更新日期:2016-06-01 00:00:00

  • Extracellular Vesicles Secreted by Human Adipose-derived Stem Cells (hASCs) Improve Survival Rate of Rats with Acute Liver Failure by Releasing lncRNA H19.

    abstract::It has previously been reported that human adipose-derived stem cells (hASCs) can promote the regeneration of damaged tissues in rats with liver failure through a 'paracrine effect'. Here we demonstrate a therapeutic effect of hASCs derived Extracellular Vesicles (EVs) on rat models with acute liver failure, as shown ...


    pub_type: 杂志文章


    authors: Jin Y,Wang J,Li H,Gao S,Shi R,Yang D,Wang X,Wang X,Zhu L,Wang X,Chen C,Ning K,Gao Z,Xu J,Fu Q

    更新日期:2018-08-01 00:00:00

  • Childhood growth and neurocognition are associated with distinct sets of metabolites.

    abstract:BACKGROUND:Undernutrition is a serious global problem that contributes to increased child morbidity and mortality, impaired neurocognitive development, and decreased educational and economic attainment. Current interventions are only marginally effective, and identification of associated metabolic pathways can offer ne...


    pub_type: 杂志文章


    authors: Moreau GB,Ramakrishnan G,Cook HL,Fox TE,Nayak U,Ma JZ,Colgate ER,Kirkpatrick BD,Haque R,Petri WA Jr

    更新日期:2019-06-01 00:00:00

  • SARS-CoV-2 leads to a small vessel endotheliitis in the heart.

    abstract:BACKGROUND:SARS-CoV-2 infection (COVID-19 disease) can induce systemic vascular involvement contributing to morbidity and mortality. SARS-CoV-2 targets epithelial and endothelial cells through the ACE2 receptor. The anatomical involvement of the coronary tree is not explored yet. METHODS:Cardiac autopsy tissue of the ...


    pub_type: 杂志文章


    authors: Maccio U,Zinkernagel AS,Shambat SM,Zeng X,Cathomas G,Ruschitzka F,Schuepbach RA,Moch H,Varga Z

    更新日期:2021-01-01 00:00:00

  • Analysis of gene expression signatures identifies prognostic and functionally distinct ovarian clear cell carcinoma subtypes.

    abstract:BACKGROUND:Ovarian clear cell carcinoma (OCCC) is a histological subtype of epithelial ovarian cancer (EOC) with distinct pathological, biological, and molecular features. OCCCs are more resistant to conventional treatment regimen of EOC and have the worst stage-adjusted prognosis amongst EOC subtypes. As the OCCC inci...


    pub_type: 杂志文章


    authors: Tan TZ,Ye J,Yee CV,Lim D,Ngoi NYL,Tan DSP,Huang RY

    更新日期:2019-12-01 00:00:00

  • Heterologous Two-Dose Vaccination with Simian Adenovirus and Poxvirus Vectors Elicits Long-Lasting Cellular Immunity to Influenza Virus A in Healthy Adults.

    abstract:BACKGROUND:T-cell responses against highly conserved influenza antigens have been previously associated with protection. However, these immune responses are poorly maintained following recovery from influenza infection and are not boosted by inactivated influenza vaccines. We have previously demonstrated the safety and...


    pub_type: 杂志文章


    authors: Coughlan L,Sridhar S,Payne R,Edmans M,Milicic A,Venkatraman N,Lugonja B,Clifton L,Qi C,Folegatti PM,Lawrie AM,Roberts R,de Graaf H,Sukhtankar P,Faust SN,Lewis DJM,Lambe T,Hill A,Gilbert SC

    更新日期:2018-03-01 00:00:00

  • TP63 isoform expression is linked with distinct clinical outcomes in cancer.

    abstract:BACKGROUND:Half of muscle-invasive bladder cancer patients will relapse with metastatic disease and molecular tests to predict relapse are needed. TP63 has been proposed as a prognostic biomarker in bladder cancer, but reports associating it with clinical outcomes are conflicting. Since TP63 is expressed as multiple is...


    pub_type: 杂志文章


    authors: Bankhead A 3rd,McMaster T,Wang Y,Boonstra PS,Palmbos PL

    更新日期:2020-01-01 00:00:00

  • Large Isoform of Mammalian Relative of DnaJ is a Major Determinant of Human Susceptibility to HIV-1 Infection.

    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...


    pub_type: 杂志文章


    authors: Chiang YP,Sheng WH,Shao PL,Chi YH,Chen YM,Huang SW,Shih HM,Chang LY,Lu CY,Chang SC,Hung CC,Huang LM

    更新日期:2014-10-07 00:00:00

  • HIV-1 Promotes the Degradation of Components of the Type 1 IFN JAK/STAT Pathway and Blocks Anti-viral ISG Induction.

    abstract::Anti-retroviral therapy successfully suppresses HIV-1 infection, but fails to provide a cure. During infection Type 1 IFNs normally play an essential role in viral clearance, but in vivo IFN-α only has a modest impact on HIV-1 infection, suggesting its possible targeting by HIV. Here, we report that the HIV protein, V...


    pub_type: 杂志文章


    authors: Gargan S,Ahmed S,Mahony R,Bannan C,Napoletano S,O'Farrelly C,Borrow P,Bergin C,Stevenson NJ

    更新日期:2018-04-01 00:00:00

  • O-glycans truncation modulates gastric cancer cell signaling and transcription leading to a more aggressive phenotype.

    abstract:BACKGROUND:Changes in glycosylation are known to play critical roles during gastric carcinogenesis. Expression of truncated O-glycans, such as the Sialyl-Tn (STn) antigen, is a common feature shared by many cancers and is associated with cancer aggressiveness and poor-prognosis. METHODS:Glycoengineered cell lines were...


    pub_type: 杂志文章


    authors: Freitas D,Campos D,Gomes J,Pinto F,Macedo JA,Matos R,Mereiter S,Pinto MT,Polónia A,Gartner F,Magalhães A,Reis CA

    更新日期:2019-02-01 00:00:00

  • Discovery and Validation of Predictive Biomarkers of Survival for Non-small Cell Lung Cancer Patients Undergoing Radical Radiotherapy: Two Proteins With Predictive Value.

    abstract::Lung cancer is the most frequent cause of cancer-related death world-wide. Radiotherapy alone or in conjunction with chemotherapy is the standard treatment for locally advanced non-small cell lung cancer (NSCLC). Currently there is no predictive marker with clinical utility to guide treatment decisions in NSCLC patien...


    pub_type: 杂志文章


    authors: Walker MJ,Zhou C,Backen A,Pernemalm M,Williamson AJ,Priest LJ,Koh P,Faivre-Finn C,Blackhall FH,Dive C,Whetton AD

    更新日期:2015-06-19 00:00:00

  • Gut Microbiota Linked to Sexual Preference and HIV Infection.

    abstract::The precise effects of HIV-1 on the gut microbiome are unclear. Initial cross-sectional studies provided contradictory associations between microbial richness and HIV serostatus and suggested shifts from Bacteroides to Prevotella predominance following HIV-1 infection, which have not been found in animal models or in ...


    pub_type: 杂志文章


    authors: Noguera-Julian M,Rocafort M,Guillén Y,Rivera J,Casadellà M,Nowak P,Hildebrand F,Zeller G,Parera M,Bellido R,Rodríguez C,Carrillo J,Mothe B,Coll J,Bravo I,Estany C,Herrero C,Saz J,Sirera G,Torrela A,Navarro J,Cre

    更新日期:2016-01-28 00:00:00

  • Splicing modulation as novel therapeutic strategy against diffuse malignant peritoneal mesothelioma.

    abstract:INTRODUCTION:Therapeutic options for diffuse malignant peritoneal mesothelioma (DMPM) are limited to surgery and locoregional chemotherapy. Despite improvements in survival rates, patients eventually succumb to disease progression. We investigated splicing deregulation both as molecular prognostic factor and potential ...


    pub_type: 杂志文章


    authors: Sciarrillo R,Wojtuszkiewicz A,El Hassouni B,Funel N,Gandellini P,Lagerweij T,Buonamici S,Blijlevens M,Zeeuw van der Laan EA,Zaffaroni N,Deraco M,Kusamura S,Würdinger T,Peters GJ,Molthoff CFM,Jansen G,Kaspers GJL,Cloos J

    更新日期:2019-01-01 00:00:00

  • Memory B Cells are Major Targets for Effective Immunotherapy in Relapsing Multiple Sclerosis.

    abstract::Although multiple sclerosis (MS) is considered to be a CD4, Th17-mediated autoimmune disease, supportive evidence is perhaps circumstantial, often based on animal studies, and is questioned by the perceived failure of CD4-depleting antibodies to control relapsing MS. Therefore, it was interestingly to find that curren...


    pub_type: 杂志文章,评审


    authors: Baker D,Marta M,Pryce G,Giovannoni G,Schmierer K

    更新日期:2017-02-01 00:00:00

  • Reduced Intellectual Ability in Offspring of Ovarian Hyperstimulation Syndrome: A Cohort Study.

    abstract:BACKGROUND:Ovarian hyperstimulation syndrome (OHSS), a complication of ovarian stimulation, has various adverse effects on both pregnant women and their offspring. However, whether OHSS will affect intellectual ability in offspring is still unknown. METHODS:We recruited 86 Chinese children born to OHSS women and 172 c...


    pub_type: 杂志文章


    authors: Xu GF,Zhou CL,Xiong YM,Li JY,Yu TT,Tian S,Lin XH,Liao Y,Lv Y,Zhang FH,Liu ZW,Shi YY,Shen Y,Sha J,Zhang D,Zhu YM,Sheng JZ,Huang HF

    更新日期:2017-06-01 00:00:00

  • Successful Treatment of Intracranial Glioblastoma Xenografts With a Monoamine Oxidase B-Activated Pro-Drug.

    abstract::The last major advance in the treatment of glioblastoma multiforme (GBM) was the introduction of temozolomide in 1999. Treatment with temozolomide following surgical debulking extends survival rate compared to radiotherapy and debulking alone. However, virtually all glioblastoma patients experience disease progression...


    pub_type: 杂志文章


    authors: Sharpe MA,Livingston AD,Gist TL,Ghosh P,Han J,Baskin DS

    更新日期:2015-08-08 00:00:00

  • Endothelial FAM3A positively regulates post-ischaemic angiogenesis.

    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 ...


    pub_type: 杂志文章


    authors: Xu W,Liang M,Zhang Y,Huang K,Wang C

    更新日期:2019-05-01 00:00:00

  • Kininogen supports inflammation and bacterial spreading during Streptococccus Pyogenes Sepsis.

    abstract:BACKGROUND:High-molecular-weight kininogen is a cofactor of the human contact system, an inflammatory response mechanism that is activated during sepsis. It has been shown that high-molecular-weight kininogen contributes to endotoxemia, but is not critical for local host defense during pneumonia by Gram-negative bacter...


    pub_type: 杂志文章


    authors: Köhler J,Maletzki C,Koczan D,Frank M,Springer A,Steffen C,Revenko AS,MacLeod AR,Mikkat S,Kreikemeyer B,Oehmcke-Hecht S

    更新日期:2020-08-01 00:00:00

  • Accumulation of mitochondrial 7S DNA in idiopathic and LRRK2 associated Parkinson's disease.

    abstract:BACKGROUND:Both idiopathic and familial Parkinson's disease are associated with mitochondrial dysfunction. Mitochondria have their own mitochondrial DNA (mtDNA) and previous studies have reported that the release of mtDNA is a biomarker of Parkinson's disease. METHODS:We have now investigated the relationship between ...


    pub_type: 杂志文章


    authors: Podlesniy P,Puigròs M,Serra N,Fernández-Santiago R,Ezquerra M,Tolosa E,Trullas R

    更新日期:2019-10-01 00:00:00

  • Reversing Gut Damage in HIV Infection: Using Non-Human Primate Models to Instruct Clinical Research.

    abstract::Antiretroviral therapy (ART) has led to dramatic improvements in the lives of HIV-infected persons. However, residual immune activation, which persists despite ART, is associated with increased risk of non-AIDS morbidities. Accumulating evidence shows that disruption of the gut mucosal epithelium during SIV/HIV infect...


    pub_type: 杂志文章,评审


    authors: Ponte R,Mehraj V,Ghali P,Couëdel-Courteille A,Cheynier R,Routy JP

    更新日期:2016-01-26 00:00:00

  • Genetics Variants and Serum Levels of MHC Class I Chain-related A in Predicting Hepatocellular Carcinoma Development in Chronic Hepatitis C Patients Post Antiviral Treatment.

    abstract:BACKGROUND/AIMS:The genome-wide association study has shown that MHC class I chain-related A (MICA) genetic variants were associated with hepatitis C virus (HCV) related hepatocellular carcinoma (HCC). The impact of the genetic variants and its serum levels on post-treatment cohort is elusive [corrected]. METHODS:MICA...


    pub_type: 杂志文章


    authors: Huang CF,Huang CY,Yeh ML,Wang SC,Chen KY,Ko YM,Lin CC,Tsai YS,Tsai PC,Lin ZY,Chen SC,Dai CY,Huang JF,Chuang WL,Yu ML

    更新日期:2017-02-01 00:00:00

  • Poor Penetration of Antibiotics Into Pericardium in Pericardial Tuberculosis.

    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...


    pub_type: 杂志文章


    authors: Shenje J,Ifeoma Adimora-Nweke F,Ross IL,Ntsekhe M,Wiesner L,Deffur A,McIlleron HM,Pasipanodya J,Gumbo T,Mayosi BM

    更新日期:2015-09-16 00:00:00

  • Targeting allosteric site of AKT by 5,7-dimethoxy-1,4-phenanthrenequinone suppresses neutrophilic inflammation.

    abstract:BACKGROUND:Acute lung injury (ALI) is a severe life-threatening inflammatory disease. Neutrophil activation is a major pathogenic factor in ALI. Protein kinase B (PKB)/AKT regulates diverse cellular responses, but the significance in neutrophilic inflammation and ALI remains unknown. METHODS:Human neutrophils and neut...


    pub_type: 杂志文章


    authors: Chen PJ,Ko IL,Lee CL,Hu HC,Chang FR,Wu YC,Leu YL,Wu CC,Lin CY,Pan CY,Tsai YF,Hwang TL

    更新日期:2019-02-01 00:00:00