2024
Charting the metabolic biogeography of the colorectum in cancer: challenging the right sided versus left sided classification
Jain A, Morris M, Berardi D, Arora T, Domingo-Almenara X, Paty P, Rattray N, Kerekes D, Lu L, Khan S, Johnson C. Charting the metabolic biogeography of the colorectum in cancer: challenging the right sided versus left sided classification. Molecular Cancer 2024, 23: 211. PMID: 39342363, PMCID: PMC11438248, DOI: 10.1186/s12943-024-02133-5.Peer-Reviewed Original ResearchMeSH KeywordsAgedBiomarkers, TumorColorectal NeoplasmsFemaleHumansMaleMetabolomeMetabolomicsMiddle AgedRectumConceptsRectal cancerNormal mucosaMetabolite abundancePatient-matched tumorTumor-specific metabolitesMetabolic heterogeneityPatient survivalRectosigmoid colonSigmoid colonAnatomic subsitePatient-matched normal mucosaTransverse colonMetabolomic profilesAscending colonCRC biomarkersMetabolome DatabaseDescending colonMetabolite changesLeft-sidedRight-sidedColorectumRisk factorsMetabolome mapCancerTumorGrowth 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
2023
Perfluorooctanesulfonic Acid and Perfluorooctanoic Acid Promote Migration of Three-Dimensional Colorectal Cancer Spheroids
Zheng J, Sun B, Berardi D, Lu L, Yan H, Zheng S, Aladelokun O, Xie Y, Cai Y, Pollitt K, Khan S, Johnson C. Perfluorooctanesulfonic Acid and Perfluorooctanoic Acid Promote Migration of Three-Dimensional Colorectal Cancer Spheroids. Environmental Science And Technology 2023, 57: 21016-21028. PMID: 38064429, DOI: 10.1021/acs.est.3c04844.Peer-Reviewed Original ResearchMeSH KeywordsAlkanesulfonic AcidsCaprylatesColorectal NeoplasmsFluorocarbonsHumansProto-Oncogene Proteins p21(ras)ConceptsColorectal cancerFatty acid β-oxidationCell linesSW48 cell linesSynthesis of proteinsProgression of CRCMigration phenotypeCRC cell linesEpithelial-mesenchymal transitionThree-dimensional spheroidsMetabolic pathwaysN-cadherinΒ-oxidationMechanism of actionNovel insightsE-cadherinBiological techniquesPromotes MigrationColorectal cancer spheroidsMigration assaysMetabolic profilingKRAS G12APerfluorooctanoic acidPersistent environmental contaminantsMetabolic profileDiscovery of decreased ferroptosis in male colorectal cancer patients with KRAS mutations
Yan H, Talty R, Jain A, Cai Y, Zheng J, Shen X, Muca E, Paty P, Bosenberg M, Khan S, Johnson C. Discovery of decreased ferroptosis in male colorectal cancer patients with KRAS mutations. Redox Biology 2023, 62: 102699. PMID: 37086630, PMCID: PMC10172914, DOI: 10.1016/j.redox.2023.102699.Peer-Reviewed Original ResearchMeSH KeywordsCell Line, TumorColorectal NeoplasmsFemaleFerroptosisHumansMaleMetabolomicsPrognosisProto-Oncogene Proteins p21(ras)Sex FactorsConceptsKRAS mutant tumorsMale CRC patientsCRC patientsMale patientsKRAS mutationsMutant tumorsOverall survivalMale colorectal cancer patientsKRAS wild-type tumorsAberrant tumor metabolismColorectal cancer patientsCRC patient cohortsColorectal cancer casesFerroptosis-related genesWild-type tumorsNovel potential avenuesNormal colon tissuesPoor OSKRAS statusAdverse outcomesCRC cellsPatient cohortCancer patientsType tumorsCancer casesEarly-Onset Colorectal Cancer Somatic Gene Mutations by Population Subgroups.
Shen X, DeWan A, Johnson C. Early-Onset Colorectal Cancer Somatic Gene Mutations by Population Subgroups. Cancer Discovery 2023, 13: 530-531. PMID: 36855917, DOI: 10.1158/2159-8290.cd-22-1464.Peer-Reviewed Original ResearchFerroptosis in colorectal cancer: a future target?
Yan H, Talty R, Aladelokun O, Bosenberg M, Johnson C. Ferroptosis in colorectal cancer: a future target? British Journal Of Cancer 2023, 128: 1439-1451. PMID: 36703079, PMCID: PMC10070248, DOI: 10.1038/s41416-023-02149-6.Peer-Reviewed Original ResearchConceptsColorectal cancerRegulated cell deathCurrent treatment optionsForms of RCDCancer deathTreatment optionsCRC therapyCancer recurrenceTreatment strategiesRadiation therapyOvert toxicityTherapeutic targetDrug resistanceTherapyCancer cellsFerroptosisPotential roleCancerCell deathFuture targetsDeathRecent studiesBiological pathwaysChemotherapySurgery
2022
Targeting ferroptosis to treat colorectal cancer
Yan H, Talty R, Johnson C. Targeting ferroptosis to treat colorectal cancer. Trends In Cell Biology 2022, 33: 185-188. PMID: 36473802, DOI: 10.1016/j.tcb.2022.11.003.Peer-Reviewed Original ResearchConceptsProtein kinase BArachidonic acidColorectal cancer treatmentProtein kinaseKinase BMammalian targetKey pathwaysGlutathione metabolismFerroptosis inductionEnergy metabolismCRC treatmentColorectal cancerCRC pathogenesisFerroptosisCancer treatmentPromising targetNew conceptual avenuesMetabolismTreatmentHippoKinasePrimary strategyRapamycinTargetConceptual avenuesBile acid distributions, sex-specificity, and prognosis in colorectal cancer
Cai Y, Shen X, Lu L, Yan H, Huang H, Gaule P, Muca E, Theriot CM, Rattray Z, Rattray NJW, Lu J, Ahuja N, Zhang Y, Paty PB, Khan SA, Johnson CH. Bile acid distributions, sex-specificity, and prognosis in colorectal cancer. Biology Of Sex Differences 2022, 13: 61. PMID: 36274154, PMCID: PMC9590160, DOI: 10.1186/s13293-022-00473-9.Peer-Reviewed Original ResearchConceptsLeft-sided colon tumorsRight-sided colon tumorsColon cancer patientsColorectal cancerTumor locationBile acidsColon tumorsCancer patientsQuantitative immunofluorescencePrimary tumor locationImmune regulatory cellsRecurrence-free survivalBile acid metabolismSecondary bile acidsBile acid distributionBile acid analysisBackgroundBile acidsOverall survivalRegulatory cellsCRC patientsMale patientsPatient sexImmune cellsPatient prognosisImmune responseDevelopment of an Accessible Gene Expression Bioinformatics Pipeline to Study Driver Mutations of Colorectal Cancer
van den Driest L, Johnson CH, Rattray NJW, Rattray Z. Development of an Accessible Gene Expression Bioinformatics Pipeline to Study Driver Mutations of Colorectal Cancer. Alternatives To Laboratory Animals 2022, 50: 282-292. PMID: 35765262, DOI: 10.1177/02611929221107546.Peer-Reviewed Original ResearchConceptsColorectal cancerBioinformatics toolsExpression patternsKirsten rat sarcoma viral oncogene homologueNext-generation sequencing technologiesDifferential expression patternsCancer-related mortalityGenetic alterationsAdenomatous polyposis coliEffector proteinsMutational driversPrognostic significancePrognostic valueSequencing technologiesBioinformatics pipelinePatient prognosisGenetic dataB-RafColorectal tumorsNovel biomarkersColon cancerTherapeutic outcomesFrequency of mutationsAnatomical locationOncogene homologue
2021
Immune landscape and prognostic immune-related genes in KRAS-mutant colorectal cancer patients
Liu J, Huang X, Liu H, Wei C, Ru H, Qin H, Lai H, Meng Y, Wu G, Xie W, Mo X, Johnson CH, Zhang Y, Tang W. Immune landscape and prognostic immune-related genes in KRAS-mutant colorectal cancer patients. Journal Of Translational Medicine 2021, 19: 27. PMID: 33413474, PMCID: PMC7789428, DOI: 10.1186/s12967-020-02638-9.Peer-Reviewed Original ResearchMeSH KeywordsAntigens, NeoplasmColonic NeoplasmsColorectal NeoplasmsGenes, rasHumansMutationPrognosisProto-Oncogene Proteins p21(ras)RelaxinTumor MicroenvironmentConceptsKRAS mutant CRC patientsTumor-infiltrating immune cellsKRAS wild-type CRC patientsCD4 memory T cellsCRC patientsMemory T cellsColorectal cancerT cellsImmune pathwaysImmune cellsMacrophage M1Hypersensitive C-reactive proteinKRAS-mutant colorectal cancerCases of CRCKRAS mutantPrognostic immune-related genesImmune risk modelColorectal cancer patientsRegulatory T cellsC-reactive proteinTumor immune microenvironmentDistinct clinical outcomesT cell receptorImmune-related genesConclusionsKRAS mutation
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 mutationsSex Differences in Colon Cancer Metabolism Reveal A Novel Subphenotype
Cai Y, Rattray NJW, Zhang Q, Mironova V, Santos-Neto A, Hsu KS, Rattray Z, Cross JR, Zhang Y, Paty PB, Khan SA, Johnson CH. Sex Differences in Colon Cancer Metabolism Reveal A Novel Subphenotype. Scientific Reports 2020, 10: 4905. PMID: 32184446, PMCID: PMC7078199, DOI: 10.1038/s41598-020-61851-0.Peer-Reviewed Original ResearchConceptsRight-sided colon cancerColorectal cancerCRC patientsColon cancer metabolismPoor clinical outcomePatient colon tumorsAsparagine synthetase expressionNovel subphenotypesClinical outcomesAmino acid uptakePoor survivalLower incidenceAnatomic locationHigh incidenceTherapeutic targetColon cancerCancer Genomic AtlasClinical importanceColon tumorsTumor progressionAberrant metabolismNormal tissuesPatientsSubphenotypesAcid uptake