2024
Growth characteristics of HCT116 xenografts lacking asparagine synthetase vary according to sex
Aladelokun O, Lu L, Zheng J, Yan H, Jain A, Gibson J, Khan S, Johnson C. Growth characteristics of HCT116 xenografts lacking asparagine synthetase vary according to sex. Human Genomics 2024, 18: 67. PMID: 38886847, PMCID: PMC11184737, DOI: 10.1186/s40246-024-00635-3.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAspartate-Ammonia LigaseCarbon-Nitrogen Ligases with Glutamine as Amide-N-DonorCell ProliferationColorectal NeoplasmsFemaleGene Expression Regulation, NeoplasticHCT116 CellsHeterograftsHumansMaleMiceReceptors, EstrogenReceptors, G-Protein-CoupledSex FactorsXenograft Model Antitumor AssaysConceptsFemale tumor-bearing miceFemale CRC patientsTumor-bearing miceCRC patientsTumor growthInferior survivalAssociated with inferior survivalMetabolic reprogrammingG protein-coupled estrogen receptorTriggering metabolic reprogrammingSustained tumor growthSuppressed tumor growthExpression of asparagine synthetaseCancer cell linesBackgroundSex-related differencesSurvival improvementImpact of sexFemale miceEstrogen receptorCancer growthTranslational relevanceRewiring of metabolic pathwaysCancer burdenMetabolic pathwaysAsparagine synthetase
2020
Gene Alterations of N6‐Methyladenosine (m6A) Regulators in Colorectal Cancer: A TCGA Database Study
Zhang Q, Cai Y, Kurbatov V, Khan SA, Lu L, Zhang Y, Johnson CH. Gene Alterations of N6‐Methyladenosine (m6A) Regulators in Colorectal Cancer: A TCGA Database Study. BioMed Research International 2020, 2020: 8826456. PMID: 33415160, PMCID: PMC7769650, DOI: 10.1155/2020/8826456.Peer-Reviewed Original ResearchMeSH KeywordsAdenosineAgedAlpha-Ketoglutarate-Dependent Dioxygenase FTOColorectal NeoplasmsDatabases, GeneticDisease-Free SurvivalDNA Copy Number VariationsFemaleGene Expression Regulation, NeoplasticGenes, NeoplasmHumansMaleMultivariate AnalysisMutationNerve Tissue ProteinsPrognosisProportional Hazards ModelsRNA Splicing FactorsRNA, MessengerConceptsDisease-free survivalImmune cell infiltrationM6A regulatorsCRC patientsCRC casesCell infiltrationMRNA expressionWorse overall survivalN6-methyladenosine regulatorsMicrosatellite instability statusMessenger RNA expressionCancer Genome AtlasOverall survivalColorectal cancerCRC tissuesDatabase studyImmune functionInstability statusColon tissuesRole of m6AGene alterationsRNA expressionCRCGenome AtlasGenetic mutationsMeta-analysis of the clinicopathological significance of miRNA-145 in breast cancer
Lv P, Zhang Z, Hou L, Zhang Y, Lu L, Wang C, Shi F. Meta-analysis of the clinicopathological significance of miRNA-145 in breast cancer. Bioscience Reports 2020, 40: bsr20193974. PMID: 32869851, PMCID: PMC7502658, DOI: 10.1042/bsr20193974.Peer-Reviewed Original ResearchMeSH KeywordsBiomarkers, TumorBreastBreast NeoplasmsFemaleGene Expression Regulation, NeoplasticHumansLymphatic MetastasisMicroRNAsTumor BurdenConceptsMiR-145 expressionBreast cancer patientsBreast cancerStandardized mean differenceBreast cancer tissuesAdjacent normal tissuesMiR-145Cancer patientsTumor suppressor miRNACancer tissuesLow expressionNormal tissuesLymph node metastasisUnfavorable prognostic factorLargest tumor diameterSuppressor miRNALower miR-145Normal breast tissueWeb of ScienceNode metastasisPrognostic factorsHealthy womenTumor diameterClinicopathological significanceEligible studiesSyndecan-1 and KRAS Gene Expression Signature Associates With Patient Survival in Pancreatic Cancer.
Wu Y, Huang H, Fervers B, Lu L. Syndecan-1 and KRAS Gene Expression Signature Associates With Patient Survival in Pancreatic Cancer. Pancreas 2020, 49: 1187-1194. PMID: 32898003, DOI: 10.1097/mpa.0000000000001654.Peer-Reviewed Original ResearchMeSH KeywordsAgedDNA MethylationFemaleGene Expression ProfilingGene Expression Regulation, NeoplasticHumansKaplan-Meier EstimateMaleMiddle AgedMutationPancreatic NeoplasmsProportional Hazards ModelsProto-Oncogene Proteins p21(ras)RNA, MessengerSyndecan-1ConceptsSyndecan-1Patient survivalPancreatic cancerAdjusted hazard ratioPancreatic cancer patientsKRAS somatic mutationsSDC1 mRNASomatic mutationsHazard ratioCancer patientsClinical dataSurvival analysisKRASPatientsKyoto EncyclopediaKRAS mRNAElevated mortalityGenomes (KEGG) pathway analysisCancerPathway analysisLower methylationMolecular characteristicsSurvivalMRNANegative correlationMicroRNA‑34a expression affects breast cancer invasion in vitro and patient survival via downregulation of E2F1 and E2F3 expression.
Han R, Zhao J, Lu L. MicroRNA‑34a expression affects breast cancer invasion in vitro and patient survival via downregulation of E2F1 and E2F3 expression. Oncology Reports 2020, 43: 2062-2072. PMID: 32186770, DOI: 10.3892/or.2020.7549.Peer-Reviewed Original ResearchMeSH KeywordsBreast NeoplasmsCell MovementCell ProliferationE2F1 Transcription FactorE2F3 Transcription FactorFemaleGene Expression Regulation, NeoplasticHumansMicroRNAsNeoplasm InvasivenessSurvival AnalysisConceptsBreast cancerNormal breast tissueMDA-MB-231 cellsPatient survivalT-47DKaplan-Meier survival curvesBreast tissueCancer-associated mortalityLonger survival timeCommon cancer typesExpression levelsReverse transcription-quantitative PCRPotential therapeutic toolBreast cancer invasionMicroRNA-34a expressionTranscription-quantitative PCRTumor cell proliferationOverall survivalUnderlying molecular mechanismsCaspase-3 activityDownregulation of E2F1Clinical managementExpression of E2F1Survival timeClinical relevance
2019
Transfer RNA methyltransferase gene NSUN2 mRNA expression modifies the effect of T cell activation score on patient survival in head and neck squamous carcinoma
Lu L, Gaffney SG, Cannataro VL, Townsend J. Transfer RNA methyltransferase gene NSUN2 mRNA expression modifies the effect of T cell activation score on patient survival in head and neck squamous carcinoma. Oral Oncology 2019, 101: 104554. PMID: 31887619, PMCID: PMC7273869, DOI: 10.1016/j.oraloncology.2019.104554.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overBiomarkersFemaleGene Expression Regulation, NeoplasticHumansKaplan-Meier EstimateLymphocyte ActivationMaleMethyltransferasesMiddle AgedNeoplasm GradingNeoplasm StagingPrognosisProportional Hazards ModelsSquamous Cell Carcinoma of Head and NeckT-LymphocytesYoung AdultConceptsT cell activation scoreT cell activation statusAdjusted hazard ratioPatient survivalHPV statusHazard ratioActivation statusActivation scoresKaplan-Meier survival curvesImmune checkpoint blockadeCox regression modelNeck squamous carcinomaPotential therapeutic targetT cell activationHNSCC patientsSquamous carcinomaPatient mortalityLonger survivalExhaustion groupsTherapeutic targetSurvival curvesSignificant associationMRNA expressionPatientsSurvivalBRCA1 mRNA expression modifies the effect of T cell activation score on patient survival in breast cancer
Lu L, Huang H, Zhou J, Ma W, Mackay S, Wang Z. BRCA1 mRNA expression modifies the effect of T cell activation score on patient survival in breast cancer. BMC Cancer 2019, 19: 387. PMID: 31023256, PMCID: PMC6482542, DOI: 10.1186/s12885-019-5595-3.Peer-Reviewed Original ResearchConceptsT cell activation statusCell activation statusPatient survivalT cell activationBreast cancerActivation statusCCND1 levelsCell activationT cell activation scoreCCND1 expressionKaplan-Meier survival curvesAdjusted hazard ratioCCND1 expression levelsBreast cancer patient survivalImmune checkpoint blockadeBetter overall survivalBreast cancer patientsCox regression modelCancer patient survivalT cell recognitionBRCA1 levelsBRCA1 mRNA expressionCheckpoint blockadeHazard ratioOverall survival
2017
IFNγ enhances cytotoxic efficiency of the cytotoxic T lymphocytes against human glioma cells
Shao S, Risch E, Burner D, Lu L, Minev B, Ma W. IFNγ enhances cytotoxic efficiency of the cytotoxic T lymphocytes against human glioma cells. International Immunopharmacology 2017, 47: 159-165. PMID: 28410529, DOI: 10.1016/j.intimp.2017.04.003.Peer-Reviewed Original ResearchConceptsCytotoxic T lymphocytesPositive glioma cellsT cell activation scoreMHC class IGlioma cellsClass IT lymphocytesTumor antigen-specific cytotoxic T lymphocytesAntigen-specific cytotoxic T lymphocytesIFNγ treatmentActivity of CTLHuman dendritic cellsRisk of deathHuman leukocyte antigenActivation scoresLow-grade gliomasMHC class I moleculesClass I moleculesHuman glioma cellsCytotoxic efficiencyDendritic cellsTumor immunityLeukocyte antigenCancer immunotherapyGlioma patients
2015
Circulating tumor cell clusters-associated gene plakoglobin and breast cancer survival
Lu L, Zeng H, Gu X, Ma W. Circulating tumor cell clusters-associated gene plakoglobin and breast cancer survival. Breast Cancer Research And Treatment 2015, 151: 491-500. PMID: 25957595, DOI: 10.1007/s10549-015-3416-1.Peer-Reviewed Original ResearchMeSH KeywordsBreast NeoplasmsCell AdhesionCell Transformation, NeoplasticFemaleGamma CateninGene Expression Regulation, NeoplasticHumansNeoplasm MetastasisNeoplastic Cells, CirculatingPrognosisSignal TransductionConceptsBreast cancer survivalCancer survivalBreast cancerTumor cellsDisease-specific deathBreast cancer recurrencePotential prognostic biomarkerBreast cancer metastasisEpithelial-mesenchymal transitionHigh metastatic potentialFurther metastasesPatient survivalCancer recurrencePrognostic biomarkerTherapeutic targetSurvival analysisMetastatic potentialCancer metastasisMajor causeHigh expressionEpithelial cellsCancerRole of plakoglobinDouble-edged functionSurvivalMicroRNA let‐7a modifies the effect of self‐renewal gene HIWI on patient survival of epithelial ovarian cancer
Lu L, Katsaros D, Risch HA, Canuto EM, Biglia N, Yu H. MicroRNA let‐7a modifies the effect of self‐renewal gene HIWI on patient survival of epithelial ovarian cancer. Molecular Carcinogenesis 2015, 55: 357-365. PMID: 25630839, DOI: 10.1002/mc.22285.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overArgonaute ProteinsCarcinoma, Ovarian EpithelialFemaleGene Expression Regulation, NeoplasticHumansKaplan-Meier EstimateMicroRNAsMiddle AgedNeoplasms, Glandular and EpithelialOvarian NeoplasmsOvaryPrognosisConceptsEpithelial ovarian cancerKaplan-Meier survival curvesOverall survivalHIWI expressionLet-7a expressionPatient survivalLet-7aClinical relevanceMultivariate Cox proportional hazards regression analysisCox proportional hazards regression analysisCox proportional hazards regression modelSurvival curvesProportional hazards regression analysisProportional hazards regression modelsLow let-7aHazards regression analysisRisk of deathPoor overall survivalHazards regression modelsMiRNA let-7aPrimary EOC tissuesQuantitative reverse transcription PCRU-shape associationEOC prognosisPrognostic significance
2014
Regulation of tumor cell migration and invasion by the H19/let-7 axis is antagonized by metformin-induced DNA methylation
Yan L, Zhou J, Gao Y, Ghazal S, Lu L, Bellone S, Yang Y, Liu N, Zhao X, Santin AD, Taylor H, Huang Y. Regulation of tumor cell migration and invasion by the H19/let-7 axis is antagonized by metformin-induced DNA methylation. Oncogene 2014, 34: 3076-3084. PMID: 25088204, DOI: 10.1038/onc.2014.236.Peer-Reviewed Original ResearchMeSH KeywordsCell Line, TumorCell MovementDNA MethylationEndometrial NeoplasmsFemaleGene Expression Regulation, NeoplasticHEK293 CellsHumansMetforminMicroRNAsNeoplasm InvasivenessOvarian NeoplasmsRNA, Long NoncodingSignal TransductionConceptsTumor cell migrationDNA methylationCell migrationTumor suppressorH19/letPotent tumor suppressorExpression of oncogenesDiverse human cancersMetastasis-promoting genesAnti-diabetic drug metforminLet-7C-MycHuman cancersH19Cell growthNovel mechanismEndometrial cancerPoor prognosisRegulationDrug metforminMethylationTherapeutic opportunitiesSuppressorTumor cellsOncogeneThe KRAS-Variant and miRNA Expression in RTOG Endometrial Cancer Clinical Trials 9708 and 9905
Lee LJ, Ratner E, Uduman M, Winter K, Boeke M, Greven KM, King S, Burke TW, Underhill K, Kim H, Boulware RJ, Yu H, Parkash V, Lu L, Gaffney D, Dicker AP, Weidhaas J. The KRAS-Variant and miRNA Expression in RTOG Endometrial Cancer Clinical Trials 9708 and 9905. PLOS ONE 2014, 9: e94167. PMID: 24732316, PMCID: PMC3986055, DOI: 10.1371/journal.pone.0094167.Peer-Reviewed Original ResearchConceptsEndometrial cancer riskType 2 endometrial cancerEndometrial cancerKRAS-variantCancer riskLymphovascular invasionSurvival outcomesTumor biologyType 1 endometrial cancerEndometrial cancer trialsOverall survival rateMiRNA expressionAge-matched controlsCase-control analysisFunctional germline variantsClinical characteristicsPatient ageTumor characteristicsCancer trialsTumor specimensSurvival rateType 1Germline variantsMiRNA expression levelsCancer
2013
An insulin-like growth factor-II intronic variant affects local DNA conformation and ovarian cancer survival
Lu L, Risch E, Deng Q, Biglia N, Picardo E, Katsaros D, Yu H. An insulin-like growth factor-II intronic variant affects local DNA conformation and ovarian cancer survival. Carcinogenesis 2013, 34: 2024-2030. PMID: 23677070, DOI: 10.1093/carcin/bgt168.Peer-Reviewed Original ResearchConceptsInsulin-like growth factor IIIGF-II expressionPatient survivalGrowth factor IIPresence of carboplatinChemotherapy responseOvarian cancerCox proportional hazards regression modelKaplan-Meier survival curvesProportional hazards regression modelsFactor IIOvarian cancer tissue samplesIGF-II genotypeAdjusted hazard ratioOvarian cancer survivalHazards regression modelsCommercial enzyme-linked immunosorbentQuantitative reverse transcription polymerase chain reactionReverse transcription-polymerase chain reactionOvarian cancer developmentTranscription-polymerase chain reactionCancer tissue samplesEnzyme-linked immunosorbentHazard ratioSNP genotyping assays
2012
Association of large noncoding RNA HOTAIR expression and its downstream intergenic CpG island methylation with survival in breast cancer
Lu L, Zhu G, Zhang C, Deng Q, Katsaros D, Mayne ST, Risch HA, Mu L, Canuto EM, Gregori G, Benedetto C, Yu H. Association of large noncoding RNA HOTAIR expression and its downstream intergenic CpG island methylation with survival in breast cancer. Breast Cancer Research And Treatment 2012, 136: 875-883. PMID: 23124417, DOI: 10.1007/s10549-012-2314-z.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overBreast NeoplasmsCpG IslandsDNA MethylationFemaleGene Expression Regulation, NeoplasticHumansMiddle AgedMultivariate AnalysisPrognosisProportional Hazards ModelsRNA, Long NoncodingSomatomedinsYoung AdultConceptsPrimary breast cancerBreast cancerHOTAIR expressionPathologic featuresCox proportional hazards regression modelProportional hazards regression modelsLow HOTAIR expressionUnfavorable disease characteristicsHazards regression modelsIndependent prognostic markerHigh HOTAIR expressionBreast cancer progressionQuantitative RT-PCRPatient survivalDisease characteristicsMethylation-specific PCRPrognostic markerLower riskSignificant associationRNA HOTAIRCancerCancer progressionBiologic relevanceRT-PCRDNA methylationLin28 regulates HER2 and promotes malignancy through multiple mechanisms
Feng C, Neumeister V, Ma W, Xu J, Lu L, Bordeaux J, Maihle NJ, Rimm DL, Huang Y. Lin28 regulates HER2 and promotes malignancy through multiple mechanisms. Cell Cycle 2012, 11: 2486-2494. PMID: 22713243, DOI: 10.4161/cc.20893.Peer-Reviewed Original ResearchMeSH KeywordsAdultBreast NeoplasmsCell Line, TumorCell ProliferationCohort StudiesFemaleGene Expression Regulation, NeoplasticHumansMiddle AgedReceptor, ErbB-2RNA-Binding ProteinsRNA, MessengerSurvival AnalysisConceptsHuman epidermal growth factor receptor 2HER2 expressionLin28 expressionEpidermal growth factor receptor 2Growth factor receptor 2Primary breast tumorsFactor receptor 2Cancer cell growthMajor therapeutic targetMultiple mechanismsAdvanced human malignanciesClinical outcomesPoor prognosisBreast cancerReceptor 2Therapeutic targetBreast tumorsNovel mechanistic insightsHuman malignanciesLin28 overexpressionReceptor tyrosine kinasesCancerCell proliferationHuman cancersPowerful predictorFavorable outcome associated with an IGF-1 ligand signature in breast cancer
Mu L, Tuck D, Katsaros D, Lu L, Schulz V, Perincheri S, Menato G, Scarampi L, Harris L, Yu H. Favorable outcome associated with an IGF-1 ligand signature in breast cancer. Breast Cancer Research And Treatment 2012, 133: 321-331. PMID: 22297468, DOI: 10.1007/s10549-012-1952-5.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overBreast NeoplasmsCarcinoma, Ductal, BreastCarcinoma, LobularCohort StudiesDisease-Free SurvivalFemaleGene ExpressionGene Expression ProfilingGene Expression Regulation, NeoplasticGene Regulatory NetworksHumansInsulin-Like Growth Factor Binding ProteinsInsulin-Like Growth Factor IKaplan-Meier EstimateLigandsMiddle AgedMultivariate AnalysisNeoplasm Recurrence, LocalOligonucleotide Array Sequence AnalysisPrognosisReceptor, IGF Type 1Young AdultConceptsIGF-1 ligandBreast cancerFavorable outcomeInsulin-like growth factor (IGF) axisActivation signaturePrimary breast cancerGrowth factor axisPredictors of responseHuman breast cancerPathway analysisUpregulation of pathwaysBetter prognosisIGF axisPrognostic valueReceptor levelsLevels of mRNAFactor axisIGF ligandsIngenuity softwarePathway activation scoresCancerLigand levelsActivation scoresHigh groupProliferation pathways
2011
Physical activity and breast cancer survival: an epigenetic link through reduced methylation of a tumor suppressor gene L3MBTL1
Zeng H, Irwin ML, Lu L, Risch H, Mayne S, Mu L, Deng Q, Scarampi L, Mitidieri M, Katsaros D, Yu H. Physical activity and breast cancer survival: an epigenetic link through reduced methylation of a tumor suppressor gene L3MBTL1. Breast Cancer Research And Treatment 2011, 133: 127-135. PMID: 21837478, DOI: 10.1007/s10549-011-1716-7.Peer-Reviewed Original ResearchMeSH KeywordsBreast NeoplasmsCarcinoma, Ductal, BreastCarcinoma, LobularChromosomal Proteins, Non-HistoneDNA MethylationEpigenesis, GeneticFemaleGene ExpressionGene Expression ProfilingGene Expression Regulation, NeoplasticGenes, Tumor SuppressorHumansKaplan-Meier EstimateMotor ActivityRepressor ProteinsTumor Suppressor ProteinsConceptsBreast cancer patientsBreast cancer survivalCancer patientsPhysical activityOverall survivalSurvival outcomesTumor suppressor geneCancer survivalHormone receptor-positive tumorsModerate-intensity aerobic exerciseHigh expressionBreast cancer deathsReceptor-positive tumorsRandomized clinical trialsExercise-related changesSuppressor genePeripheral blood leukocytesBreast cancer diagnosisGene expressionDisease recurrenceAerobic exerciseCancer deathClinical trialsTumor featuresBlood leukocytes
2010
IGF-II promoter specific methylation and expression in epithelial ovarian cancer and their associations with disease characteristics.
Qian B, Katsaros D, Lu L, Canuto EM, Benedetto C, Beeghly-Fadiel A, Yu H. IGF-II promoter specific methylation and expression in epithelial ovarian cancer and their associations with disease characteristics. Oncology Reports 2010, 25: 203-13. PMID: 21109978, PMCID: PMC3075064, DOI: 10.3892/or_00001062.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overDisease-Free SurvivalDNA MethylationFemaleGene Expression Regulation, NeoplasticHumansInsulin-Like Growth Factor IIMiddle AgedNeoplasm StagingNeoplasms, Glandular and EpithelialOvarian NeoplasmsPromoter Regions, GeneticReverse Transcriptase Polymerase Chain ReactionConceptsInsulin-like growth factor IIEpithelial ovarian cancerOvarian cancerDisease progressionResidual tumor sizeIGF-II peptideFresh tumor samplesIGF-II expressionPromoter-specific expressionIGF-II mRNAGrowth factor IIIGF-II promotersLower mRNA expressionOverall survivalAggressive diseasePoor prognosisTumor sizeDisease characteristicsMethylation-specific PCRTumor gradeTreatment responseIGF-II transcriptionPromoter-specific methylationClinical implicationsCancerLet-7a regulation of insulin-like growth factors in breast cancer
Lu L, Katsaros D, Zhu Y, Hoffman A, Luca S, Marion CE, Mu L, Risch H, Yu H. Let-7a regulation of insulin-like growth factors in breast cancer. Breast Cancer Research And Treatment 2010, 126: 687-694. PMID: 20848182, DOI: 10.1007/s10549-010-1168-5.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overBreast NeoplasmsDNA MethylationEnzyme-Linked Immunosorbent AssayGene Expression Regulation, NeoplasticHeLa CellsHumansMicroRNAsMiddle AgedPrognosisReverse Transcriptase Polymerase Chain ReactionSomatomedinsConceptsIGF expressionBreast cancerOvarian cancerInsulin-like growth factorDisease-free survivalCancer cellsAction of IGFBreast cancer patientsExpression of IGFHigh-grade tumorsIGF-II expressionPR-negative cancerLet-7aQuantitative methylation-specific PCRBreast cancer samplesOverall survivalFavorable prognosisPatient survivalCancer patientsGrade tumorsIGF mRNAsMethylation-specific PCRDisease featuresCancerCancer samples
2008
High miR-21 expression in breast cancer associated with poor disease-free survival in early stage disease and high TGF-β1
Qian B, Katsaros D, Lu L, Preti M, Durando A, Arisio R, Mu L, Yu H. High miR-21 expression in breast cancer associated with poor disease-free survival in early stage disease and high TGF-β1. Breast Cancer Research And Treatment 2008, 117: 131-140. PMID: 18932017, DOI: 10.1007/s10549-008-0219-7.Peer-Reviewed Original ResearchConceptsMiR-21 expressionPoor disease-free survivalHigh miR-21 expressionDisease-free survivalHormone receptor statusHigh miR-21Breast cancerMiR-21Tumor samplesReceptor statusTumor gradeTGF-β1Elevated miR-21 expressionNegative hormone receptor statusProportional hazards regression analysisHigher TGF-β1Lymph node involvementEarly-stage diseaseEarly-stage patientsPrimary breast cancerHazards regression analysisHigh tumor gradeFresh tumor samplesTumor cell growthNode involvement