2024
GP100 expression is variable in intensity in melanoma
Mann J, Hasson N, Su D, Adeniran A, Smalley K, Djureinovic D, Jilaveanu L, Schoenfeld D, Kluger H. GP100 expression is variable in intensity in melanoma. Cancer Immunology, Immunotherapy 2024, 73: 191. PMID: 39105816, PMCID: PMC11303354, DOI: 10.1007/s00262-024-03776-5.Peer-Reviewed Original ResearchConceptsGp100 expressionCutaneous melanomaTreatment of cutaneous melanomaAdvanced cutaneous melanomaT-cell engagersImprove patient selectionMetastatic melanomaUveal melanomaMetastatic samplesPatient selectionClinical trialsMelanomaQuantitative immunofluorescence methodGp100Improve outcomesImmunofluorescence methodTherapeutic intentDrugCellular productsExpressionTebentafuspImmunohistochemistryMelanocortin-1 Receptor Expression as a Marker of Progression in Melanoma
Su D, Djureinovic D, Schoenfeld D, Marquez-Nostra B, Olino K, Jilaveanu L, Kluger H. Melanocortin-1 Receptor Expression as a Marker of Progression in Melanoma. JCO Precision Oncology 2024, 8: e2300702. PMID: 38662983, DOI: 10.1200/po.23.00702.Peer-Reviewed Original ResearchConceptsMC1R expressionMelanoma progressionAssociated with shorter survivalStages of melanoma progressionCases of benign neviChronic sun exposureMarkers of progressionHuman melanoma tissuesBreslow thicknessMelanocortin-1Metastatic melanomaOverall survivalPrimary melanomaMetastatic tumorsMelanoma cohortReceptor expressionPredictive biomarkersAggressive melanomaPrimary lesionTissue microarrayShorter survivalMale sexQuantitative immunofluorescenceBenign neviClinical trialsDigital spatial proteomic profiling reveals immune checkpoints as biomarkers in lymphoid aggregates and tumor microenvironment of desmoplastic melanoma
Su D, Schoenfeld D, Ibrahim W, Cabrejo R, Djureinovic D, Baumann R, Rimm D, Khan S, Halaban R, Kluger H, Olino K, Galan A, Clune J. Digital spatial proteomic profiling reveals immune checkpoints as biomarkers in lymphoid aggregates and tumor microenvironment of desmoplastic melanoma. Journal For ImmunoTherapy Of Cancer 2024, 12: e008646. PMID: 38519058, PMCID: PMC10961546, DOI: 10.1136/jitc-2023-008646.Peer-Reviewed Original ResearchConceptsCTLA-4 expression levelsCancer-associated fibroblastsAssociated with worse survivalExpression of immune checkpointsLAG-3 expressionDesmoplastic melanomaLymphoid aggregatesCTLA-4PD-1Immune checkpointsIntratumoral leukocytesLAG-3Tumor compartmentsWorse survivalCD20+B cellsIncreased expression of immune checkpointsProgrammed cell death protein 1Macrophage/monocyte markerSentinel lymph node positivityCell death protein 1Associated with poor prognosisLymph node positivityDense fibrous stromaPotential prognostic significanceCore of tumors
2021
Infiltration of NK and plasma cells is associated with a distinct immune subset in non‐small cell lung cancer
Backman M, La Fleur L, Kurppa P, Djureinovic D, Elfving H, Brunnström H, Mattsson J, Lindberg A, Pontén V, Eltahir M, Mangsbo S, Gulyas M, Isaksson J, Jirström K, Kärre K, Leandersson K, Mezheyeuski A, Pontén F, Strell C, Lindskog C, Botling J, Micke P. Infiltration of NK and plasma cells is associated with a distinct immune subset in non‐small cell lung cancer. The Journal Of Pathology 2021, 255: 243-256. PMID: 34339045, DOI: 10.1002/path.5772.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerImmune cell infiltrationHigh immune cell infiltrationCell infiltrationNK cellsImmune classPlasma cellsLow immune cell infiltrationEra of immunotherapyCell lung cancerImmune cell markersTumor mutational loadImmune response-related genesInnate immune responseImmune cell analysisClinicopathologic characteristicsPD-L1Immune activationImmune classificationNSCLC casesImmune patternsLung cancerImmune cellsClinical backgroundImmune response
2019
A clonal expression biomarker associates with lung cancer mortality
Biswas D, Birkbak N, Rosenthal R, Hiley C, Lim E, Papp K, Boeing S, Krzystanek M, Djureinovic D, La Fleur L, Greco M, Döme B, Fillinger J, Brunnström H, Wu Y, Moore D, Skrzypski M, Abbosh C, Litchfield K, Al Bakir M, Watkins T, Veeriah S, Wilson G, Jamal-Hanjani M, Moldvay J, Botling J, Chinnaiyan A, Micke P, Hackshaw A, Bartek J, Csabai I, Szallasi Z, Herrero J, McGranahan N, Swanton C. A clonal expression biomarker associates with lung cancer mortality. Nature Medicine 2019, 25: 1540-1548. PMID: 31591602, PMCID: PMC6984959, DOI: 10.1038/s41591-019-0595-z.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerClinicopathological risk factorsCell lung cancerLung cancer mortalityPrognostic gene expression signaturesCancer cell proliferationGene expression signaturesCancer mortalityLung cancerRisk factorsExpression-based biomarkersCopy number gainsDisease subtypesClinical descriptorsTranscriptomic biomarkersIndividual tumorsCancer typesDiagnostic precisionMolecular biomarkersExpression signaturesCell proliferationDNA copy number gainsBiomarkersPatientsIntratumor heterogeneityMultiplex plasma protein profiling identifies novel markers to discriminate patients with adenocarcinoma of the lung
Djureinovic D, Pontén V, Landelius P, Al Sayegh S, Kappert K, Kamali-Moghaddam M, Micke P, Ståhle E. Multiplex plasma protein profiling identifies novel markers to discriminate patients with adenocarcinoma of the lung. BMC Cancer 2019, 19: 741. PMID: 31357969, PMCID: PMC6664554, DOI: 10.1186/s12885-019-5943-3.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinoma of LungAgedBlood ProteinsCarcinoembryonic AntigenCarcinoma, Non-Small-Cell LungChemokines, CXCCohort StudiesData AccuracyEarly Detection of CancerFemaleGPI-Linked ProteinsHumansImmunoassayLung NeoplasmsMaleMass ScreeningModels, BiologicalReceptor, ErbB-3ROC CurveSensitivity and SpecificityStatistics, NonparametricVascular Endothelial Growth Factor Receptor-2ConceptsNon-small cell lung cancerProximity extension assayLung adenocarcinomaLung diseaseDisease groupNon-malignant lung diseasesEarly lung cancer detectionCell lung cancerDifferent lung diseasesDifferent plasma levelsMultiplex proximity extension assayHigh clinical relevanceNovel protein markersDifferent plasma concentrationsLocalized diseaseOverall prognosisSurgical resectionNSCLC patientsLung metastasesColorectal cancerLung cancerPlasma levelsTypical carcinoidLung conditionsLAC patientsPrognostic Impact of Tumor Cell Programmed Death Ligand 1 Expression and Immune Cell Infiltration in NSCLC
Edlund K, Madjar K, Mattsson J, Djureinovic D, Lindskog C, Brunnström H, Koyi H, Brandén E, Jirström K, Pontén F, Rahnenführer J, Micke P, Hengstler J. Prognostic Impact of Tumor Cell Programmed Death Ligand 1 Expression and Immune Cell Infiltration in NSCLC. Journal Of Thoracic Oncology 2019, 14: 628-640. PMID: 30639618, DOI: 10.1016/j.jtho.2018.12.022.Peer-Reviewed Original ResearchConceptsPD-L1 positivityOverall survivalLymphocyte infiltrationSmoking historyPD-L1Prognostic associationPlasma cellsProgrammed Death Ligand 1 ExpressionTumor PD-L1 positivityDeath ligand 1 (PD-L1) expressionAssociation of lymphocytePositive immune cellsLigand 1 expressionPD-L1 axisPD-L1 statusMultivariate Cox regressionDeath ligand 1Longer overall survivalForkhead box P3Immune cell infiltrationShorter overall survivalPatients' smoking historyKaplan-Meier plotsCheckpoint inhibitorsNSCLC patients
2018
Detection of autoantibodies against cancer-testis antigens in non-small cell lung cancer
Djureinovic D, Dodig-Crnković T, Hellström C, Holgersson G, Bergqvist M, Mattsson J, Pontén F, Ståhle E, Schwenk J, Micke P. Detection of autoantibodies against cancer-testis antigens in non-small cell lung cancer. Lung Cancer 2018, 125: 157-163. PMID: 30429015, DOI: 10.1016/j.lungcan.2018.09.012.Peer-Reviewed Original ResearchConceptsCancer-testis antigensLung cancer patientsNSCLC patientsCancer patientsNon-small cell lung cancer patientsNon-small cell lung cancerCell lung cancer patientsLin-28 homolog BPresence of autoantibodiesCell lung cancerBenign lung diseasesDetection of autoantibodiesFamily member 3Immune targetsLung diseaseLung cancerNSCLC samplesImmune responseAutoantibodiesBenign groupPatientsBead arrayBead array technologyAntigenMember A (Fam46a) geneAn Integrative Analysis of Transcriptome and Epigenome Features of ASCL1–Positive Lung Adenocarcinomas
Miyashita N, Horie M, Suzuki H, Yoshihara M, Djureinovic D, Persson J, Brunnström H, Lindskog C, Elfving H, Micke P, Saito A, Nagase T. An Integrative Analysis of Transcriptome and Epigenome Features of ASCL1–Positive Lung Adenocarcinomas. Journal Of Thoracic Oncology 2018, 13: 1676-1691. PMID: 30121393, DOI: 10.1016/j.jtho.2018.07.096.Peer-Reviewed Original ResearchConceptsAchaete-scute family bHLH transcription factor 1Transcriptome profilingGenome-wide epigenetic profilingRecent transcriptome profilingGenome-wide methylation analysisFamily bHLH transcription factor 1Cell cycle controlMaster transcriptional regulatorGene expression profilingGlobal DNA hypomethylationLung adenocarcinomaEpigenome featuresTranscription factor 1Transcriptional regulatorsTranscriptional programsCancer Genome AtlasEpigenetic profilingLung adenocarcinoma cellsMolecular featuresExpression profilingCycle controlDNA hypomethylationIntegrative analysisMethylation analysisCell death ligand-1 (PD-L1) protein expressionExpression of scavenger receptor MARCO defines a targetable tumor‐associated macrophage subset in non‐small cell lung cancer
La Fleur L, Boura V, Alexeyenko A, Berglund A, Pontén V, Mattsson J, Djureinovic D, Persson J, Brunnström H, Isaksson J, Brandén E, Koyi H, Micke P, Karlsson M, Botling J. Expression of scavenger receptor MARCO defines a targetable tumor‐associated macrophage subset in non‐small cell lung cancer. International Journal Of Cancer 2018, 143: 1741-1752. PMID: 29667169, DOI: 10.1002/ijc.31545.Peer-Reviewed Original ResearchConceptsTumor-associated macrophagesHigher macrophage infiltrationScavenger receptor MARCOPD-L1Macrophage infiltrationNon-small cell lung cancer (NSCLC) cohortMajority of TAMsNon-small cell lung cancerAvailable immune checkpoint inhibitorsCell lung cancer cohortTumor-associated macrophage subsetsImmunosuppressive tumor-associated macrophagesNew immune targetsImmune checkpoint inhibitorsImmune checkpoint moleculesT cell infiltrationDeath ligand 1Cell lung cancerLung cancer cohortSubset of casesImmune response pathwaysExpression of MARCOProtumor phenotypeCheckpoint inhibitorsCheckpoint moleculesMultispectral imaging for quantitative and compartment‐specific immune infiltrates reveals distinct immune profiles that classify lung cancer patients
Mezheyeuski A, Bergsland C, Backman M, Djureinovic D, Sjöblom T, Bruun J, Micke P. Multispectral imaging for quantitative and compartment‐specific immune infiltrates reveals distinct immune profiles that classify lung cancer patients. The Journal Of Pathology 2018, 244: 421-431. PMID: 29282718, DOI: 10.1002/path.5026.Peer-Reviewed Original ResearchMeSH KeywordsBiomarkers, TumorCarcinoma, Non-Small-Cell LungClinical Decision-MakingDeep LearningFluorescent Antibody TechniqueHumansImage Interpretation, Computer-AssistedLung NeoplasmsLymphocyte SubsetsLymphocytes, Tumor-InfiltratingMicroscopy, FluorescencePredictive Value of TestsPrognosisReproducibility of ResultsSequence Analysis, RNATissue Array AnalysisTumor MicroenvironmentConceptsImmune infiltratesImmune markersImmune cellsImmunohistochemical methodsEra of immunotherapyCell lung cancerImmune cell infiltrationLymphocyte subclassesNSCLC casesCell infiltrationLung cancerPatient prognosisImmune responseTissue microarrayCancer tissuesStromal compartmentClinical decisionFurther subpopulationSemiquantitative assessmentConventional immunohistochemistryImmunohistochemistryClinical biopsiesTissue sectionsFoxp3CD4
2017
A pathology atlas of the human cancer transcriptome
Uhlen M, Zhang C, Lee S, Sjöstedt E, Fagerberg L, Bidkhori G, Benfeitas R, Arif M, Liu Z, Edfors F, Sanli K, von Feilitzen K, Oksvold P, Lundberg E, Hober S, Nilsson P, Mattsson J, Schwenk J, Brunnström H, Glimelius B, Sjöblom T, Edqvist P, Djureinovic D, Micke P, Lindskog C, Mardinoglu A, Ponten F. A pathology atlas of the human cancer transcriptome. Science 2017, 357 PMID: 28818916, DOI: 10.1126/science.aan2507.Peer-Reviewed Original ResearchConceptsRegulation of genesGenome-scale metabolic modelProtein-coding genesGenome-wide transcriptomeHuman cancer transcriptomeGenome-wide explorationCellular differentiationIndividual proteinsCancer transcriptomeMolecular mechanismsMetabolic modelsCell growthGenesTranscriptomeOpen-access databaseSystem-level approachMajor cancer typesMetabolic heterogeneityPathology AtlasGeneral patternCancer typesRegulationShorter patient survivalIndividual tumorsProteinPD-L1 immunohistochemistry in clinical diagnostics of lung cancer: inter-pathologist variability is higher than assay variability
Brunnström H, Johansson A, Westbom-Fremer S, Backman M, Djureinovic D, Patthey A, Isaksson-Mettävainio M, Gulyas M, Micke P. PD-L1 immunohistochemistry in clinical diagnostics of lung cancer: inter-pathologist variability is higher than assay variability. Modern Pathology 2017, 30: 1411-1421. PMID: 28664936, DOI: 10.1038/modpathol.2017.59.Peer-Reviewed Original ResearchConceptsPositive tumor cellsTumor cellsLung cancerPD-L1 checkpoint inhibitorsPD-L1 assaysPD-L1 immunohistochemistryCell death 1Squamous cell carcinomaPD-L1 scoresLung cancer casesCheckpoint inhibitorsDeath-1Cell carcinomaClinical studiesCancer casesImmunohistochemical stainingTissue microarrayInterrater variationAntibody 22C3Cutoff levelInter-pathologist variabilityTumor tissueClinical settingSP142Antibody clonesReaching the limits of prognostication in non-small cell lung cancer: an optimized biomarker panel fails to outperform clinical parameters
Grinberg M, Djureinovic D, Brunnström H, Mattsson J, Edlund K, Hengstler J, La Fleur L, Ekman S, Koyi H, Branden E, Ståhle E, Jirström K, Tracy D, Pontén F, Botling J, Rahnenführer J, Micke P. Reaching the limits of prognostication in non-small cell lung cancer: an optimized biomarker panel fails to outperform clinical parameters. Modern Pathology 2017, 30: 964-977. PMID: 28281552, DOI: 10.1038/modpathol.2017.14.Peer-Reviewed Original ResearchMeSH KeywordsBiomarkers, TumorCarcinoma, Non-Small-Cell LungCell Adhesion Molecule-1Enhancer of Zeste Homolog 2 ProteinGlucose Transporter Type 1HumansImmunohistochemistryIntracellular Signaling Peptides and ProteinsLung NeoplasmsNuclear ProteinsPrognosisThyroid Nuclear Factor 1Tissue Array AnalysisConceptsNon-small cell lung cancerCell lung cancerNon-small cell lung cancer patientsCell lung cancer patientsLung cancer patientsLung cancerBiomarker panelClinical parametersCancer patientsPrognostic associationClinicopathological parametersClinical practicePrognostic modelSurvival predictionProtein expressionBest prognostic modelPrognostic biomarker panelBetter prognostic performanceImmunohistochemistry-based assessmentCorresponding concordance indexProtein biomarkersClinicopathological dataConcordance indexPrognostic performanceTissue microarrayA systematic search strategy identifies cubilin as independent prognostic marker for renal cell carcinoma
Gremel G, Djureinovic D, Niinivirta M, Laird A, Ljungqvist O, Johannesson H, Bergman J, Edqvist P, Navani S, Khan N, Patil T, Sivertsson Å, Uhlén M, Harrison D, Ullenhag G, Stewart G, Pontén F. A systematic search strategy identifies cubilin as independent prognostic marker for renal cell carcinoma. BMC Cancer 2017, 17: 9. PMID: 28052770, PMCID: PMC5215231, DOI: 10.1186/s12885-016-3030-6.Peer-Reviewed Original ResearchConceptsRenal cell carcinomaCell carcinomaClear cell RCC patientsPrimary renal cell carcinomaPositive prognostic indicatorIndependent prognostic markerUnmet clinical needMalignant human tissuesNew diagnostic markersVenous tumorNodal statusBetter prognosisMetastatic lesionsNegative tumorsSystematic search strategyT stagePatient survivalPoor prognosisPositive tumorsRCC patientsPrognostic indicatorFuhrman gradePrognostic markerRCC cohortTissue microarray
2016
The Human Adrenal Gland Proteome Defined by Transcriptomics and Antibody-Based Profiling
Bergman J, Botling J, Fagerberg L, Hallström B, Djureinovic D, Uhlén M, Pontén F. The Human Adrenal Gland Proteome Defined by Transcriptomics and Antibody-Based Profiling. Endocrinology 2016, 158: 239-251. PMID: 27901589, DOI: 10.1210/en.2016-1758.Peer-Reviewed Original ResearchConceptsImmunohistochemistry-based protein profilingNormal human tissue typesProtein coding genesMessenger RNA sequencingExpression levelsProtein expression patternsHuman tissue typesCoding genesProtein homologsFERM domainRelative expression levelsCorresponding proteinRNA sequencingWide transcriptomicsExpression patternsProtein profilingGreater expression levelsGenesSpecific functionsProteinMolecular landscapeTissue typesProteomeTranscriptomicsElevated expressionProfiling cancer testis antigens in non–small-cell lung cancer
Djureinovic D, Hallström B, Horie M, Mattsson J, La Fleur L, Fagerberg L, Brunnström H, Lindskog C, Madjar K, Rahnenführer J, Ekman S, Ståhle E, Koyi H, Brandén E, Edlund K, Hengstler J, Lambe M, Saito A, Botling J, Pontén F, Uhlén M, Micke P. Profiling cancer testis antigens in non–small-cell lung cancer. JCI Insight 2016, 1: e86837. PMID: 27699219, PMCID: PMC5033889, DOI: 10.1172/jci.insight.86837.Peer-Reviewed Original ResearchConceptsCell lung cancerLung cancerCancer testisCTA expressionDifferent normal organsProtein expressionCancer Genome AtlasImmunotherapeutic strategiesPrognostic impactNSCLC casesNSCLC tissuesSurvival associationsNew CTANormal organsBiomarker studiesClinical interestCancerGenome AtlasReliable CTACTANSCLCConcurrent expressionRNAseq dataValuable targetStringent criteriaThe Impact of the Fourth Edition of the WHO Classification of Lung Tumours on Histological Classification of Resected Pulmonary NSCCs
Micke P, Mattsson J, Djureinovic D, Nodin B, Jirström K, Tran L, Jönsson P, Planck M, Botling J, Brunnström H. The Impact of the Fourth Edition of the WHO Classification of Lung Tumours on Histological Classification of Resected Pulmonary NSCCs. Journal Of Thoracic Oncology 2016, 11: 862-872. PMID: 26872818, DOI: 10.1016/j.jtho.2016.01.020.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaAdultAgedAged, 80 and overBiomarkers, TumorCarcinoma, Large CellCarcinoma, Non-Small-Cell LungCarcinoma, Squamous CellFemaleHumansImmunohistochemistryLung NeoplasmsMaleMiddle AgedNeoplasm StagingNeuroendocrine TumorsPrognosisSmall Cell Lung CarcinomaWorld Health OrganizationConceptsNon-small cell carcinomaPulmonary non-small cell carcinomaCell carcinomaWHO classificationLung tumorsFourth EditionWorld Health Organization classificationLarge cell carcinomaSquamous cell carcinomaThyroid transcription factor-1Cases of adenocarcinomaMost patientsHistological typeAdenocarcinoma groupAdenocarcinomatous differentiationOrganization classificationLung cancerNeuroendocrine tumorsTranscription factor 1Napsin AHistological classificationIHC markersHistopathological classificationImmunohistochemical stainingIHC staining
2015
Tissue-based map of the human proteome
Uhlén M, Fagerberg L, Hallström B, Lindskog C, Oksvold P, Mardinoglu A, Sivertsson Å, Kampf C, Sjöstedt E, Asplund A, Olsson I, Edlund K, Lundberg E, Navani S, Szigyarto C, Odeberg J, Djureinovic D, Takanen J, Hober S, Alm T, Edqvist P, Berling H, Tegel H, Mulder J, Rockberg J, Nilsson P, Schwenk J, Hamsten M, von Feilitzen K, Forsberg M, Persson L, Johansson F, Zwahlen M, von Heijne G, Nielsen J, Pontén F. Tissue-based map of the human proteome. Science 2015, 347: 1260419. PMID: 25613900, DOI: 10.1126/science.1260419.Peer-Reviewed Original ResearchConceptsPutative protein-coding genesHuman tissue proteomesProtein-coding genesInteractive web-based databaseIntegrated omics approachDifferent tissuesGlobal expression patternsSingle-cell levelMembrane proteomeProteome variationDruggable proteomeOmics approachesHuman proteomeHuman secretomeMolecular detailsIndividual proteinsQuantitative transcriptomicsCancer proteomeTissue proteomeProteomeExpression patternsHuman biologyMetabolic functionsTissue microarray-based immunohistochemistryMajor tissues
2014
The human testis-specific proteome defined by transcriptomics and antibody-based profiling
Djureinovic D, Fagerberg L, Hallström B, Danielsson A, Lindskog C, Uhlén M, Pontén F. The human testis-specific proteome defined by transcriptomics and antibody-based profiling. Molecular Human Reproduction 2014, 20: 476-488. PMID: 24598113, DOI: 10.1093/molehr/gau018.Peer-Reviewed Original ResearchConceptsExpression patternsAntibody-based protein profilingTestis-enriched expression patternNormal human tissue typesWide transcriptomic analysisTissue-specific genesAntibody-based profilingPutative human genesList of genesHaploid germ cellsHuman tissue typesDifferent cell typesHuman reproductive biologyReproductive biologyWide analysisProtein localizationHuman genesTranscriptomic analysisCorresponding proteinStages of spermatogenesisDeep sequencingProtein profilingMolecular understandingGerm cellsGenes