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 ResearchConceptsRectal 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 ResearchConceptsColorectal 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 profileRole of colectomy in the management of appendiceal tumors: a retrospective cohort study
Marks V, Kerekes D, Butensky S, Ahuja N, Johnson C, Turaga K, Khan S. Role of colectomy in the management of appendiceal tumors: a retrospective cohort study. BMC Gastroenterology 2023, 23: 398. PMID: 37978348, PMCID: PMC10655451, DOI: 10.1186/s12876-023-03019-4.Peer-Reviewed Original ResearchConceptsGoblet cell adenocarcinomaNon-mucinous adenocarcinomaRight hemicolectomyStage 2 diseaseNeuroendocrine neoplasmsTumor typesAppendiceal tumorsMucinous adenocarcinomaAppendiceal goblet cell adenocarcinomaRole of colectomyNational Cancer DatabasePostoperative hospital stayRetrospective cohort studyRisk-adjusted analysisRange of histologiesDifferent tumor typesConclusionsMost patientsHospital stayUnplanned readmissionCohort studySurgical treatmentHistologic typeSurgical outcomesCell adenocarcinomaCancer DatabaseMulti-omic analysis reveals metabolic pathways that characterize right-sided colon cancer liver metastasis
Morris M, Jain A, Sun B, Kurbatov V, Muca E, Zeng Z, Jin Y, Roper J, Lu J, Paty P, Johnson C, Khan S. Multi-omic analysis reveals metabolic pathways that characterize right-sided colon cancer liver metastasis. Cancer Letters 2023, 574: 216384. PMID: 37716465, PMCID: PMC10620771, DOI: 10.1016/j.canlet.2023.216384.Peer-Reviewed Original ResearchConceptsLiver metastasesColon cancer liver metastasisCancer liver metastasesSided colon cancerSubset of patientsGrowth factor betaMulti-omics analysisFatty acid oxidationMetastatic diseaseInferior survivalClinical differencesClinical behaviorUntargeted metabolomics analysisTumor behaviorColon cancerBile acidsTumor cell metabolismFactor betaPatientsMetastasisPI3K-AktReactive oxygen speciesMEK-ERKLiquid chromatography-mass spectrometryRCCSurgical treatment of stage IV gastroenteropancreatic neuroendocrine carcinoma: Experience and outcomes in the United States
Kerekes D, Frey A, Bakkila B, Kunstman J, Khan S. Surgical treatment of stage IV gastroenteropancreatic neuroendocrine carcinoma: Experience and outcomes in the United States. Journal Of Surgical Oncology 2023, 128: 790-802. PMID: 37435780, DOI: 10.1002/jso.27392.Peer-Reviewed Original ResearchConceptsGastroenteropancreatic neuroendocrine carcinomasGEP-NECSingle-site surgeryOverall survivalSurgical treatmentNeuroendocrine carcinomaMortality reductionSite surgeryPrimary siteNational Cancer DatabaseRetrospective cohort studyPrimary tumor typeSurgical resectionCohort studyAggressive diseaseSurgical interventionSurvival outcomesTreatment optionsCancer DatabaseSurgeryPatientsTumor typesNECStrongest predictorCarcinomaDiscovery 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 ResearchConceptsKRAS 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 casesImpact of nonmalignant ascites on outcomes of open inguinal hernia repair in the USA
Kerekes D, Sznol J, Khan S, Becher R. Impact of nonmalignant ascites on outcomes of open inguinal hernia repair in the USA. Hernia 2023, 27: 1497-1506. PMID: 37029887, DOI: 10.1007/s10029-023-02790-3.Peer-Reviewed Original ResearchConceptsOpen inguinal herniorrhaphyOdds of mortalityInguinal hernia repairSerious complicationsInguinal herniorrhaphyNonelective repairElective repairAscites patientsHernia repairSurgeons National Surgical Quality Improvement Program databaseNational Surgical Quality Improvement Program databaseQuality Improvement Program databaseOpen inguinal hernia repairImpact of ascitesNational US databasePrimary end pointImprovement Program databaseRetrospective cohort studyChallenging clinical dilemmaPreoperative ascitesCohort studyComposite outcomeNonelective surgeryPoor outcomeSurgical outcomesIn silico designed mRNA vaccines targeting CA-125 neoantigen in breast and ovarian cancer
Lu L, Ma W, Johnson C, Khan S, Irwin M, Pusztai L. In silico designed mRNA vaccines targeting CA-125 neoantigen in breast and ovarian cancer. Vaccine 2023, 41: 2073-2083. PMID: 36813666, PMCID: PMC10064809, DOI: 10.1016/j.vaccine.2023.02.048.Peer-Reviewed Original ResearchConceptsMRNA vaccinesOvarian cancerT cell responsesMutation-derived neoantigensT cell epitopesSARS-CoV-2Multiple neoantigensCytotoxic CD8Dendritic cellsCA 125Cancer vaccinesPatient survivalImmune responseCell epitopesNeoepitope peptidesNeoantigensVaccineCell responsesCancerBreastReverse vaccinologyCD8CD40LIFNNeoepitopes
2022
Bile 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 responseHemoglobin normalization outperforms other methods for standardizing dried blood spot metabolomics: A comparative study
Jain A, Morris M, Lin EZ, Khan SA, Ma X, Deziel NC, Godri Pollitt KJ, Johnson CH. Hemoglobin normalization outperforms other methods for standardizing dried blood spot metabolomics: A comparative study. The Science Of The Total Environment 2022, 854: 158716. PMID: 36113793, DOI: 10.1016/j.scitotenv.2022.158716.Peer-Reviewed Original ResearchEvaluation of Racial Disparities in Quality of Care for Patients With Gastrointestinal Tract Cancer Treated With Surgery
Bakkila BF, Kerekes D, Nunez-Smith M, Billingsley KG, Ahuja N, Wang K, Oladele C, Johnson CH, Khan SA. Evaluation of Racial Disparities in Quality of Care for Patients With Gastrointestinal Tract Cancer Treated With Surgery. JAMA Network Open 2022, 5: e225664. PMID: 35377425, PMCID: PMC8980937, DOI: 10.1001/jamanetworkopen.2022.5664.Peer-Reviewed Original ResearchConceptsGastrointestinal tract cancerNegative resection marginsTract cancerNegative surgical marginsBlack patientsAdequate lymphadenectomyWhite patientsQuality of careRacial disparitiesSurgical resectionResection marginsSurgical marginsSurgical careNational Cancer DatabaseRetrospective cohort studySite of cancerLonger median survivalHealth careStandard of careCommon age rangeSignificant racial disparitiesAdjuvant chemotherapyBiliary resectionAdjuvant therapyAdult patientsLipid Metabolism in Biliary Tract Cancer: A New Therapeutic Target?
Kerekes DM, Khan SA. Lipid Metabolism in Biliary Tract Cancer: A New Therapeutic Target? Annals Of Surgical Oncology 2022, 29: 2750-2751. PMID: 35243594, DOI: 10.1245/s10434-022-11383-w.Peer-Reviewed Original Research
2021
Kynurenic acid may underlie sex-specific immune responses to COVID-19
Cai Y, Kim DJ, Takahashi T, Broadhurst DI, Yan H, Ma S, Rattray NJW, Casanovas-Massana A, Israelow B, Klein J, Lucas C, Mao T, Moore AJ, Muenker MC, Oh JE, Silva J, Wong P, team Y, Ko AI, Khan SA, Iwasaki A, Johnson CH. Kynurenic acid may underlie sex-specific immune responses to COVID-19. Science Signaling 2021, 14: eabf8483. PMID: 34230210, PMCID: PMC8432948, DOI: 10.1126/scisignal.abf8483.Peer-Reviewed Original ResearchConceptsKynurenic acidImmune responseClinical outcomesSex-specific immune responsesT cell responsesPoor clinical outcomeCOVID-19 patientsCoronavirus disease 2019COVID-19Sex-related differencesMale patientsCytokine abundanceInflammatory cytokinesKynurenine ratioSerum metabolomeDisease 2019Sex-specific linkKynurenine aminotransferaseCell responsesOld malePatientsMalesOutcomesResponseMetabolitesIntratumour microbiome associated with the infiltration of cytotoxic CD8+ T cells and patient survival in cutaneous melanoma
Zhu G, Su H, Johnson CH, Khan SA, Kluger H, Lu L. Intratumour microbiome associated with the infiltration of cytotoxic CD8+ T cells and patient survival in cutaneous melanoma. European Journal Of Cancer 2021, 151: 25-34. PMID: 33962358, PMCID: PMC8184628, DOI: 10.1016/j.ejca.2021.03.053.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAgedAged, 80 and overBacteriaBacterial LoadBacterial TranslocationChemokinesClostridialesCytotoxicity, ImmunologicFemaleGastrointestinal MicrobiomeHumansLymphocyte CountLymphocytes, Tumor-InfiltratingMaleMelanomaMiddle AgedPrognosisSkin NeoplasmsT-Lymphocytes, CytotoxicTumor MicroenvironmentYoung AdultConceptsT cellsCutaneous melanomaPatient survivalGut microbiomeAdjusted hazard ratioT cell infiltrationChemokine gene expressionChemokine levelsCytotoxic CD8Hazard ratioSystemic inflammationShorter survivalCCL5 expressionPatient outcomesCD8Immune responseMortality riskGut microbiotaSurvival analysisMelanomaTumor nicheHuman cancersSurvivalSignificant correlationPositive association5‐Fluorouracil efficacy requires anti‐tumor immunity triggered by cancer‐cell‐intrinsic STING
Tian J, Zhang D, Kurbatov V, Wang Q, Wang Y, Fang D, Wu L, Bosenberg M, Muzumdar MD, Khan S, Lu Q, Yan Q, Lu J. 5‐Fluorouracil efficacy requires anti‐tumor immunity triggered by cancer‐cell‐intrinsic STING. The EMBO Journal 2021, 40: embj2020106065. PMID: 33615517, PMCID: PMC8013832, DOI: 10.15252/embj.2020106065.Peer-Reviewed Original ResearchConceptsAnti-tumor immunityTumor burdenSubsequent type I interferon productionHigh STING expressionIntratumoral T cellsT-cell depletionType I interferon productionI interferon productionLoss of STINGImmunocompetent hostsColorectal specimensT cellsSTING expressionBetter survivalHigh doseTherapeutic effectivenessHuman colorectal specimensMelanoma tumorsInterferon productionChemotherapeutic drugsMurine colonImmunityEfficacyStingsColon
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 uptakePalliative care is underutilized and affects healthcare costs in ruptured abdominal aortic aneurysms
Liu S, Heller DR, Jean RA, Chiu AS, Khan SA, Dardik A. Palliative care is underutilized and affects healthcare costs in ruptured abdominal aortic aneurysms. Surgery 2020, 168: 234-236. PMID: 32139140, PMCID: PMC7748368, DOI: 10.1016/j.surg.2020.01.017.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAgedAged, 80 and overAortic Aneurysm, AbdominalAortic RuptureCardiopulmonary ResuscitationComorbidityEndovascular ProceduresFemaleHospital ChargesHospital MortalityHumansLength of StayMaleMiddle AgedPalliative CareRenal DialysisRespiration, ArtificialTracheostomyUnited StatesYoung AdultAssociation of Treatment Inequity and Ancestry With Pancreatic Ductal Adenocarcinoma Survival
Heller DR, Nicolson NG, Ahuja N, Khan S, Kunstman JW. Association of Treatment Inequity and Ancestry With Pancreatic Ductal Adenocarcinoma Survival. JAMA Surgery 2020, 155: e195047. PMID: 31800002, PMCID: PMC6902102, DOI: 10.1001/jamasurg.2019.5047.Peer-Reviewed Original ResearchConceptsPancreatic ductal adenocarcinomaNational Cancer DatabaseWhite patientsBlack patientsAdvanced diseaseOverall survivalClinical parametersDisease stageCancer DatabaseSurgical proceduresMultivariable Cox proportional hazards regression modelingTreatment inequitiesCox proportional hazards regression modelingPancreatic ductal adenocarcinoma (PDAC) survivalUnadjusted median overall survivalYounger ageProportional hazards regression modelingMedian overall survivalModest survival advantageStage II diseaseNew cancer diagnosesLess chemotherapyResectable cancerCohort studyPrimary outcome