2024
Immune infiltration at the primary tumor is associated with clinical outcome of patients with extranodal extension of lymph node metastasis in oral cancer
Michikawa C, Gleber-Netto F, Pickering C, Rao X, Wang J, Sikora A, Myers J, Frederick M. Immune infiltration at the primary tumor is associated with clinical outcome of patients with extranodal extension of lymph node metastasis in oral cancer. Oral Oncology 2024, 153: 106729. PMID: 38663156, DOI: 10.1016/j.oraloncology.2024.106729.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedCarcinoma, Squamous CellExtranodal ExtensionFemaleHumansLymphatic MetastasisMaleMiddle AgedMouth NeoplasmsPrognosisConceptsOral cavity squamous cell carcinomaAssociated with clinical outcomesExtranodal extensionLymph node metastasisImmune infiltrationImmune infiltration statusOverall survivalPrimary tumorNode metastasisOral cancerInfiltration statusClinical outcomes of OSCC patientsExtension of lymph node metastasesAssociated with clinical outcomes of patientsAssociated with OS rateLocally advanced oral cancerClinical outcomes of patientsOutcome of OSCC patientsAssociated with poor overall survivalImmune infiltration of tumorsLow immune infiltrationNode negative tumorsAdvanced oral cancerHuman papillomavirus-negativeInfiltration of tumors
2023
Deep learning‐based pathology image analysis predicts cancer progression risk in patients with oral leukoplakia
Zhang X, Gleber‐Netto F, Wang S, Martins‐Chaves R, Gomez R, Vigneswaran N, Sarkar A, William W, Papadimitrakopoulou V, Williams M, Bell D, Palsgrove D, Bishop J, Heymach J, Gillenwater A, Myers J, Ferrarotto R, Lippman S, Pickering C, Xiao G. Deep learning‐based pathology image analysis predicts cancer progression risk in patients with oral leukoplakia. Cancer Medicine 2023, 12: 7508-7518. PMID: 36721313, PMCID: PMC10067069, DOI: 10.1002/cam4.5478.Peer-Reviewed Original ResearchConceptsLow-risk groupOral leukoplakiaOL patientsProgression riskOral mucosaHigh-risk patientsOral cancer developmentRisk stratification modelCancer progression riskLarge interobserver variabilityEarly diagnosisHigh riskDysplasia gradingAbnormal morphological featuresOral epitheliumOC developmentEarly interventionLow-risk onesPatientsStratification modelCancer developmentCancer progressionInterobserver variabilityLeukoplakiaRisk
2022
Mutant p53 drives an immune cold tumor immune microenvironment in oral squamous cell carcinoma
Shi Y, Xie T, Wang B, Wang R, Cai Y, Yuan B, Gleber-Netto FO, Tian X, Rodriguez-Rosario AE, Osman AA, Wang J, Pickering CR, Ren X, Sikora AG, Myers JN, Rangel R. Mutant p53 drives an immune cold tumor immune microenvironment in oral squamous cell carcinoma. Communications Biology 2022, 5: 757. PMID: 35902768, PMCID: PMC9334280, DOI: 10.1038/s42003-022-03675-4.Peer-Reviewed Original ResearchConceptsOral cavity squamous cell carcinomaTumor immune microenvironmentCold tumor immune microenvironmentSquamous cell carcinomaICI therapyOSCC modelCell carcinomaImmune microenvironmentCold tumorsCell death protein 1 (PD-1) inhibitorsCancer cell-intrinsic mechanismsImmune checkpoint inhibitor therapyOral squamous cell carcinomaCheckpoint inhibitor therapyCombination ICI treatmentEffective immunotherapeutic approachesInterferon genes (STING) agonistImmunosuppressive M2 macrophagesProtein 1 inhibitorTobacco-associated cancersICI responsivenessICI treatmentCell-intrinsic mechanismsImmunotherapeutic approachesInhibitor therapyFusobacterium is enriched in oral cancer and promotes induction of programmed death-ligand 1 (PD-L1)
Michikawa C, Gopalakrishnan V, Harrandah AM, Karpinets TV, Garg RR, Chu RA, Park YP, Chukkapallia SS, Yadlapalli N, Erikson-Carter KC, Gleber-Netto FO, Sayour E, Progulske-Fox A, Chan , Wu X, Zhang J, Jobin C, Wargo JA, Pickering CR, Myers JN, Silver N. Fusobacterium is enriched in oral cancer and promotes induction of programmed death-ligand 1 (PD-L1). Neoplasia 2022, 31: 100813. PMID: 35834946, PMCID: PMC9287628, DOI: 10.1016/j.neo.2022.100813.Peer-Reviewed Original ResearchConceptsPD-L1 expressionAdjacent normal tissuesWhole-exome sequencingNormal tissuesNeck cancerOral tongue squamous cell carcinoma patientsTongue squamous cell carcinoma patientsSquamous cell carcinoma patientsTumor samplesPD-L1 mRNA expressionPD-L1 protein expressionOral tongue SCCCell carcinoma patientsOral tongue cancerImmune cell infiltrationPD-L1 mRNATumor immune microenvironmentNeck SCC cell linesNeck cancer cell linesSCC cell linesDevelopment of headCell linesCancer cell linesTongue SCCCarcinoma patientsGenetic Changes Driving Immunosuppressive Microenvironments in Oral Premalignancy
Rangel R, Pickering CR, Sikora AG, Spiotto MT. Genetic Changes Driving Immunosuppressive Microenvironments in Oral Premalignancy. Frontiers In Immunology 2022, 13: 840923. PMID: 35154165, PMCID: PMC8829003, DOI: 10.3389/fimmu.2022.840923.Peer-Reviewed Original ResearchMeSH KeywordsCarcinoma, Squamous CellHumansMouth NeoplasmsPrecancerous ConditionsTumor MicroenvironmentConceptsOral premalignant lesionsImmunosuppressive microenvironmentProgression of OPLsOral cavity cancerGenomic alterationsImmune microenvironmentOral cancerOSCC progressionInflammatory environmentPremalignant lesionsSpecific genomic changesOral premalignancyTherapeutic approachesNovel biomarkersMalignant transformationMicroenvironmental changesCancerProgressionGenomic changesMicroenvironmentAlterationsGenetic changesPremalignancyTherapyLesions
2020
Functionally impactful TP53 mutations are associated with increased risk of extranodal extension in clinically advanced oral squamous cell carcinoma
Gleber‐Netto F, Neskey D, de Mattos Costa A, Kataria P, Rao X, Wang J, Kowalski LP, Pickering CR, Dias‐Neto E, Myers JN. Functionally impactful TP53 mutations are associated with increased risk of extranodal extension in clinically advanced oral squamous cell carcinoma. Cancer 2020, 126: 4498-4510. PMID: 32797678, DOI: 10.1002/cncr.33101.Peer-Reviewed Original ResearchConceptsAdvanced oral squamous cell carcinomaOral squamous cell carcinomaExtranodal extensionSquamous cell carcinomaTP53 mutationsAncillary biomarkersCell carcinomaCancer Genome Atlas (TCGA) cohortPostoperative adjuvant therapyTP53 mutation statusWild-type TP53Adjuvant therapyCancer Genome AtlasCommon genetic eventClinicopathologic characteristicsClinical outcomesP53 protein functionPatient managementTreatment decisionsClinical challengeTherapeutic approachesPatientsMutation statusHeterogeneous groupIncreased chanceLoss of p53 drives neuron reprogramming in head and neck cancer
Amit M, Takahashi H, Dragomir MP, Lindemann A, Gleber-Netto FO, Pickering CR, Anfossi S, Osman AA, Cai Y, Wang R, Knutsen E, Shimizu M, Ivan C, Rao X, Wang J, Silverman DA, Tam S, Zhao M, Caulin C, Zinger A, Tasciotti E, Dougherty PM, El-Naggar A, Calin GA, Myers JN. Loss of p53 drives neuron reprogramming in head and neck cancer. Nature 2020, 578: 449-454. PMID: 32051587, PMCID: PMC9723538, DOI: 10.1038/s41586-020-1996-3.Peer-Reviewed Original ResearchMeSH KeywordsAdrenergic AntagonistsAdrenergic NeuronsAnimalsCell DivisionCell TransdifferentiationCellular ReprogrammingDisease Models, AnimalDisease ProgressionFemaleHumansMaleMiceMice, Inbred BALB CMicroRNAsMouth NeoplasmsNerve FibersNeuritesReceptors, AdrenergicRetrospective StudiesSensory Receptor CellsTumor MicroenvironmentTumor Suppressor Protein p53Xenograft Model Antitumor AssaysConceptsOral cancerNerve fibersAdrenergic nerve fibersPoor clinical outcomeTrigeminal sensory neuronsLoss of TP53Sensory denervationAdrenergic nervesChemical sympathectomyNerve densitySensory nervesClinical outcomesSolid tumor microenvironmentLoss of p53Neck cancerPharmacological blockadeEndogenous neuronsRetrospective analysisMouse modelSensory neuronsAdrenergic phenotypeAdrenergic receptorsTumor growthTumor progressionTumor microenvironment
2019
Disruption of TP63-miR-27a* Feedback Loop by Mutant TP53 in Head and Neck Cancer
Chari NS, Ivan C, Le X, Li J, Mijiti A, Patel AA, Osman AA, Peterson CB, Williams MD, Pickering CR, Caulin C, Myers JN, Calin GA, Lai SY. Disruption of TP63-miR-27a* Feedback Loop by Mutant TP53 in Head and Neck Cancer. Journal Of The National Cancer Institute 2019, 112: 266-277. PMID: 31124563, PMCID: PMC7073912, DOI: 10.1093/jnci/djz097.Peer-Reviewed Original ResearchMeSH KeywordsCase-Control StudiesChromatin ImmunoprecipitationFeedback, PhysiologicalHead and Neck NeoplasmsHumansMicroRNAsMouth NeoplasmsMutationNeoplasm StagingPromoter Regions, GeneticSquamous Cell Carcinoma of Head and NeckSurvival RateTranscription FactorsTranscription, GeneticTumor Suppressor Protein p53Tumor Suppressor ProteinsConceptsMutant TP53Neck squamous cell carcinomaSquamous cell carcinomaHNSCC cell linesInhibits tumor growthEpidermal growth factor receptorFrequent eventRole of TP53PI3K pathwayGrowth factor receptorCancer Genome AtlasCell carcinomaNeck cancerHNSCC samplesPoor survivalEpidermal growth factorTumor growthVivo findingsTumor progressionPatient samplesTumor samplesTumor survivalTumor cellsNormal tissuesNovel target
2018
Mutation allele frequency threshold does not affect prognostic analysis using next-generation sequencing in oral squamous cell carcinoma
Ma J, Fu Y, Tu YY, Liu Y, Tan YR, Ju WT, Pickering CR, Myers JN, Zhang ZY, Zhong LP. Mutation allele frequency threshold does not affect prognostic analysis using next-generation sequencing in oral squamous cell carcinoma. BMC Cancer 2018, 18: 758. PMID: 30041611, PMCID: PMC6057048, DOI: 10.1186/s12885-018-4481-8.Peer-Reviewed Original ResearchConceptsOral squamous cell carcinomaSquamous cell carcinomaPrognostic analysisOSCC patientsCell carcinomaMethodsForty-six patientsClinical outcome analysisNext-generation sequencingAllele frequency thresholdWild-type genotypeParaffin-embedded tissuesNon-synonymous mutationsAllele frequenciesClinical outcomesOutcome analysisPatientsPanel of cancerType genotypeSignificant differencesCarcinomaFrequency thresholdNotch1CDKN2AMutationsCASP8High-Risk TP53 Mutations Are Associated with Extranodal Extension in Oral Cavity Squamous Cell Carcinoma
Sandulache VC, Michikawa C, Kataria P, Gleber-Netto FO, Bell D, Trivedi S, Rao X, Wang J, Zhao M, Jasser S, Myers JN, Pickering CR. High-Risk TP53 Mutations Are Associated with Extranodal Extension in Oral Cavity Squamous Cell Carcinoma. Clinical Cancer Research 2018, 24: 1727-1733. PMID: 29330202, PMCID: PMC5884733, DOI: 10.1158/1078-0432.ccr-17-0721.Peer-Reviewed Original ResearchConceptsOral cavity squamous cell carcinomaExtranodal extensionPrimary tumorDisease-free survivalPoor prognostic factorProspective clinical trialsSquamous cell carcinomaAggressive biological phenotypeClin Cancer ResHigh-risk mutationsPersonalized treatment decisionsWild-type TP53ENE statusOSCC dataPN0 tumorsCancer Genome AtlasLymph nodesPrognostic factorsClinical outcomesInstitutional cohortCell carcinomaClinical trialsPoor survivalTreatment decisionsTreatment selection
2017
APOBEC3A is an oral cancer prognostic biomarker in Taiwanese carriers of an APOBEC deletion polymorphism
Chen TW, Lee CC, Liu H, Wu CS, Pickering CR, Huang PJ, Wang J, Chang IY, Yeh YM, Chen CD, Li HP, Luo JD, Tan BC, Chan TEH, Hsueh C, Chu LJ, Chen YT, Zhang B, Yang CY, Wu CC, Hsu CW, See LC, Tang P, Yu JS, Liao WC, Chiang WF, Rodriguez H, Myers JN, Chang KP, Chang YS. APOBEC3A is an oral cancer prognostic biomarker in Taiwanese carriers of an APOBEC deletion polymorphism. Nature Communications 2017, 8: 465. PMID: 28878238, PMCID: PMC5587710, DOI: 10.1038/s41467-017-00493-9.Peer-Reviewed Original ResearchConceptsOral squamous cell carcinomaSquamous cell carcinomaCell carcinomaTaiwanese oral squamous cell carcinomasClinical prognostic relevanceBetter overall survivalCancer prognostic biomarkersExpression of APOBEC3AOverall survivalPrognostic relevanceTaiwanese patientsPrognostic biomarkerSecond cohortGermline polymorphismsCancer typesProminent cancerMutational profileDeletion polymorphismPatientsCarcinomaMutation signaturesExpressionPolymorphismCohortTumorsPrevalence of promoter mutations in the TERT gene in oral cavity squamous cell carcinoma
Chang K, Wang C, Pickering CR, Huang Y, Tsai C, Tsang N, Kao H, Cheng M, Myers JN. Prevalence of promoter mutations in the TERT gene in oral cavity squamous cell carcinoma. Head & Neck 2017, 39: 1131-1137. PMID: 28230921, DOI: 10.1002/hed.24728.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overCarcinoma, Squamous CellCohort StudiesDisease ProgressionDisease-Free SurvivalFemaleGene Expression Regulation, NeoplasticHumansKaplan-Meier EstimateMaleMiddle AgedMouth NeoplasmsMutationPrevalencePromoter Regions, GeneticReal-Time Polymerase Chain ReactionRetrospective StudiesRisk AssessmentStatistics, NonparametricSurvival AnalysisTaiwanTelomeraseConceptsOral cavity squamous cell carcinomaSquamous cell carcinomaTERT promoter mutationsAdjacent normal tissuesPromoter mutationsSomatic TERT promoter mutationsNormal tissuesC228T mutationTelomerase reverse transcriptase (TERT) promoterT mutationSCC tumor tissuesHuman telomerase reverse transcriptase (hTERT) promoterC250T mutationsReverse transcriptase promoterCell carcinomaSCC tumorsC228TTumor tissueTERT activityBetel nutTERT promoterTissuePresent studyMutationsSanger method
2015
New DNA Methylation Markers and Global DNA Hypomethylation Are Associated with Oral Cancer Development
Foy JP, Pickering CR, Papadimitrakopoulou VA, Jelinek J, Lin SH, William WN, Frederick MJ, Wang J, Lang W, Feng L, Zhang L, Kim ES, Fan YH, Hong WK, El-Naggar AK, Lee JJ, Myers JN, Issa JP, Lippman SM, Mao L, Saintigny P. New DNA Methylation Markers and Global DNA Hypomethylation Are Associated with Oral Cancer Development. Cancer Prevention Research 2015, 8: 1027-1035. PMID: 26342026, PMCID: PMC4777304, DOI: 10.1158/1940-6207.capr-14-0179.Peer-Reviewed Original ResearchConceptsGlobal DNA hypomethylationOral squamous cell carcinomaOral premalignant lesionsDNA hypomethylationOral cancer-free survivalCancer-free survivalDNA methylation changesDNA methylation profilesPromoter methylationDNA promoter methylationGlobal DNA methylationTumor suppressor geneNew DNA methylation markersPromoter CpG sitesOSCC developmentDNA methylationMethylation changesMethylation profilesFoxi2Degree of methylationSuppressor geneCpG sitesMethylationDNA methylation markersGenes
2013
Integrative Genomic Characterization of Oral Squamous Cell Carcinoma Identifies Frequent Somatic Drivers
Pickering CR, Zhang J, Yoo SY, Bengtsson L, Moorthy S, Neskey DM, Zhao M, Alves M, Chang K, Drummond J, Cortez E, Xie TX, Zhang D, Chung W, Issa JP, Zweidler-McKay PA, Wu X, El-Naggar AK, Weinstein JN, Wang J, Muzny DM, Gibbs RA, Wheeler DA, Myers JN, Frederick MJ. Integrative Genomic Characterization of Oral Squamous Cell Carcinoma Identifies Frequent Somatic Drivers. Cancer Discovery 2013, 3: 770-781. PMID: 23619168, PMCID: PMC3858325, DOI: 10.1158/2159-8290.cd-12-0537.Peer-Reviewed Original ResearchConceptsOral squamous cell carcinomaCaspase-8Integrative Genomic CharacterizationGenomic alterationsSquamous cell carcinomaComprehensive genomic analysisTumor suppressor geneCopy number changesSomatic driversKey genesGenomic analysisCell carcinomaGene expressionNotch pathwayGenomic characterizationSuppressor geneDriver pathwaysCopy numberPoint mutationsGenesSomatic eventsNumber changesSurvival of patientsOSCC cell linesSubset of headCT Imaging Correlates of Genomic Expression for Oral Cavity Squamous Cell Carcinoma
Pickering CR, Shah K, Ahmed S, Rao A, Frederick MJ, Zhang J, Unruh AK, Wang J, Ginsberg LE, Kumar AJ, Myers JN, Hamilton JD. CT Imaging Correlates of Genomic Expression for Oral Cavity Squamous Cell Carcinoma. American Journal Of Neuroradiology 2013, 34: 1818-1822. PMID: 23764725, PMCID: PMC7965627, DOI: 10.3174/ajnr.a3635.Peer-Reviewed Original ResearchConceptsOral cavity squamous cell carcinomaSquamous cell carcinomaEpidermal growth factor receptorGrowth factor receptorCell carcinomaGenomic biomarkersFactor receptorPrimary tumorImaging correlatesUntreated oral cavity squamous cell carcinomaRelevant genomic biomarkersVascular endothelial growth factor receptor 1Vascular endothelial growth factor receptorPrimary tumor sizeEndothelial growth factor receptorGrowth factor receptor 1Mass effectPreoperative CT imagingFactor receptor 1Untreated patientsAngiogenesis-related genesCT findingsPerineural invasionTumor sizePredictive biomarkers