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 cases
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 response
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
2019
Exploring Microsatellite Instability (MSI) in Colorectal Cancer at Elevated Microsatellite Alterations at Selected Tetranucleotides (EMAST)
Kurbatov V, Khan SA. Exploring Microsatellite Instability (MSI) in Colorectal Cancer at Elevated Microsatellite Alterations at Selected Tetranucleotides (EMAST). Annals Of Surgical Oncology 2019, 27: 973-974. PMID: 31788754, DOI: 10.1245/s10434-019-08051-x.Peer-Reviewed Original Research
2018
Regional Differences in Palliative Care Utilization Among Geriatric Colorectal Cancer Patients Needing Emergent Surgery
Heller DR, Jean RA, Chiu AS, Feder SI, Kurbatov V, Cha C, Khan SA. Regional Differences in Palliative Care Utilization Among Geriatric Colorectal Cancer Patients Needing Emergent Surgery. Journal Of Gastrointestinal Surgery 2018, 23: 153-162. PMID: 30328071, PMCID: PMC6751557, DOI: 10.1007/s11605-018-3929-0.Peer-Reviewed Original ResearchConceptsMultivariable logistic regressionPalliative careColorectal cancerPC consultationEmergent surgerySurgical patientsOstomy formationMethodsThe National Inpatient SampleLogistic regressionComplicated colorectal cancerPalliative care utilizationColorectal cancer patientsNational Inpatient SampleMeeting inclusion criteriaQuality of lifeChi-square testingCritical illnessElderly patientsHospital factorsMetastatic diseasePC patientsCare utilizationGeriatric patientsCancer patientsInpatient SampleIntegrated molecular subtyping defines a curable oligometastatic state in colorectal liver metastasis
Pitroda SP, Khodarev NN, Huang L, Uppal A, Wightman SC, Ganai S, Joseph N, Pitt J, Brown M, Forde M, Mangold K, Xue L, Weber C, Segal JP, Kadri S, Stack ME, Khan S, Paty P, Kaul K, Andrade J, White KP, Talamonti M, Posner MC, Hellman S, Weichselbaum RR. Integrated molecular subtyping defines a curable oligometastatic state in colorectal liver metastasis. Nature Communications 2018, 9: 1793. PMID: 29728604, PMCID: PMC5935683, DOI: 10.1038/s41467-018-04278-6.Peer-Reviewed Original ResearchConceptsColorectal liver metastasesLiver metastasesColorectal cancerOligometastatic colorectal cancerMetastatic colorectal cancerHigh-risk patientsSubset of patientsClinical risk stratificationTreatment of metastasesAngiogenic signatureVEGFA amplificationOligometastatic stateOverall survivalFavorable survivalRisk stratificationAdverse outcomesMetastatic cancerMolecular subtypesFocal therapyMetastasisPatientsMetastatic virulenceMolecular subtypingRobust subtypesCancer
2016
EGFR Gene Amplification and KRAS Mutation Predict Response to Combination Targeted Therapy in Metastatic Colorectal Cancer
Khan SA, Zeng Z, Shia J, Paty PB. EGFR Gene Amplification and KRAS Mutation Predict Response to Combination Targeted Therapy in Metastatic Colorectal Cancer. Pathology & Oncology Research 2016, 23: 673-677. PMID: 28025786, PMCID: PMC5451302, DOI: 10.1007/s12253-016-0166-2.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntineoplastic Agents, ImmunologicalAntineoplastic Agents, PhytogenicAntineoplastic Combined Chemotherapy ProtocolsBevacizumabBiomarkers, TumorCamptothecinCetuximabColorectal NeoplasmsDNA Mutational AnalysisErbB ReceptorsFemaleGene AmplificationGenes, p53HumansIrinotecanMaleMiddle AgedMutationRas ProteinsConceptsCombination biologic therapyMetastatic colorectal cancerIrinotecan-refractory colorectal cancerRefractory colorectal cancerColorectal cancerEGFR gene amplificationBiologic therapyKRAS mutationsIrinotecan-refractory metastatic colorectal cancerRefractory metastatic colorectal cancerCombination Targeted TherapyGene amplificationPhase II trialEGFR copy numberII trialPredictive biomarkersPredictive markerTargeted therapyTreatment responseBRAF mutationsBevacizumabPatientsCetuximabTumor tissueTherapyColorectal cancer in the very young: a comparative study of tumor markers, pathology and survival in early onset and adult onset patients
Khan SA, Morris M, Idrees K, Gimbel MI, Rosenberg S, Zeng Z, Li F, Gan G, Shia J, LaQuaglia MP, Paty PB. Colorectal cancer in the very young: a comparative study of tumor markers, pathology and survival in early onset and adult onset patients. Journal Of Pediatric Surgery 2016, 51: 1812-1817. PMID: 27558481, PMCID: PMC5312708, DOI: 10.1016/j.jpedsurg.2016.07.015.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAdolescentAdultAge of OnsetAgedAged, 80 and overBiomarkers, TumorChildColorectal NeoplasmsDNA Mismatch RepairDNA Mutational AnalysisDNA, NeoplasmFemaleHumansMaleMicrosatellite InstabilityMiddle AgedMutationNeoplasm StagingRetrospective StudiesSurvival RateUnited StatesYoung AdultConceptsOnset colorectal cancerEarly-onset colorectal cancerAdult-onset patientsColorectal cancerEarly age onsetPoor prognosisMicrosatellite instabilityOnset patientsClinical dataEarly-age onset colorectal cancerMLH1/PMS2 lossAdult colorectal cancerAdult CRC patientsAdvanced stage presentationMismatch repair expressionHigh-grade cancerAge 30 yearsSpecific genetic subtypesCRC patientsFavorable survivalPMS2 lossGrade cancerBRAF mutationsTumor markersBRAFV600E mutation
2010
Improved Testing for Microsatellite Instability in Colorectal Cancer Using a Simplified 3-Marker Assay
Esemuede I, Forslund A, Khan SA, Qin LX, Gimbel MI, Nash GM, Zeng Z, Rosenberg S, Shia J, Barany F, Paty PB. Improved Testing for Microsatellite Instability in Colorectal Cancer Using a Simplified 3-Marker Assay. Annals Of Surgical Oncology 2010, 17: 3370-3378. PMID: 20703819, PMCID: PMC3269820, DOI: 10.1245/s10434-010-1147-4.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaAdolescentAdultAgedAged, 80 and overBiological AssayBiomarkers, TumorColorectal NeoplasmsComparative Genomic HybridizationDNA RepairDNA Repair EnzymesFemaleFollow-Up StudiesGenetic TestingGerm-Line MutationHumansLymphatic MetastasisMaleMicrosatellite InstabilityMicrosatellite RepeatsMiddle AgedOligonucleotide Array Sequence AnalysisPrognosisProspective StudiesSurvival RateYoung AdultConceptsHereditary nonpolyposis colorectal cancerColorectal cancerMicrosatellite instabilityMSI testingMSI tumorsMismatch repair protein lossBackgroundIn colorectal cancerDisease-specific survivalPredictive scoring systemNonpolyposis colorectal cancerMore BRAF mutationsDefective DNA mismatch repairNCI criteriaFavorable prognosisFavorable survivalKRAS mutationsBRAF mutationsMSI statusDistinct phenotypic propertiesScoring systemCancerValuable markerMSS cancersMethodsDNA samplesProtein lossLoss of imprinting and marked gene elevation are 2 forms of aberrant IGF2 expression in colorectal cancer
Cheng Y, Idrees K, Shattock R, Khan SA, Zeng Z, Brennan CW, Paty P, Barany F. Loss of imprinting and marked gene elevation are 2 forms of aberrant IGF2 expression in colorectal cancer. International Journal Of Cancer 2010, 127: 568-577. PMID: 19957330, PMCID: PMC3270092, DOI: 10.1002/ijc.25086.Peer-Reviewed Original ResearchMeSH KeywordsColorectal NeoplasmsDNA MethylationGenomic ImprintingHumansInsulin-Like Growth Factor IIPolymorphism, GeneticPromoter Regions, GeneticConceptsInsulin-like growth factor 2IGF2 LOIColorectal cancerLoss of imprintingPrimary colorectal cancerIGF2 expressionNormal colorectal tissuesPrimary CRC tumorsSignificant correlationGrowth factor 2CRC tumorigenesisCRC tumorsIGF2 levelsColorectal tissuesIGF2 overexpressionH19 methylationHuman malignanciesMicrosatellite instabilityExpression correlatesNormal tissuesH19 hypomethylationCancerCommon eventAberrant gene expressionFactor 2
2008
CpG Island Methylator Phenotype Associates with Low-Degree Chromosomal Abnormalities in Colorectal Cancer
Cheng YW, Pincas H, Bacolod MD, Schemmann G, Giardina SF, Huang J, Barral S, Idrees K, Khan SA, Zeng Z, Rosenberg S, Notterman DA, Ott J, Paty P, Barany F. CpG Island Methylator Phenotype Associates with Low-Degree Chromosomal Abnormalities in Colorectal Cancer. Clinical Cancer Research 2008, 14: 6005-6013. PMID: 18829479, PMCID: PMC3268558, DOI: 10.1158/1078-0432.ccr-08-0216.Peer-Reviewed Original ResearchConceptsCpG island methylator phenotypeColorectal cancerChromosomal aberrationsLigase detection reactionMicrosatellite instabilityRight-side colonPrimary colorectal cancerColorectal cancer developmentSporadic colorectal cancerSame study cohortCIMP-positive tumorsChromosomal instabilityStudy cohortAberrant promoter methylationPrimary tumorNormal mucosaBRAF mutationsIndependent markerPhenotype associatesDegree of aneuploidyBRAF mutation V600ETumor progressionIndependent molecular mechanismsCancerCancer developmentc-Met gene amplification is associated with advanced stage colorectal cancer and liver metastases
Zeng ZS, Weiser MR, Kuntz E, Chen CT, Khan SA, Forslund A, Nash GM, Gimbel M, Yamaguchi Y, Culliford AT, D’Alessio M, Barany F, Paty PB. c-Met gene amplification is associated with advanced stage colorectal cancer and liver metastases. Cancer Letters 2008, 265: 258-269. PMID: 18395971, PMCID: PMC4367187, DOI: 10.1016/j.canlet.2008.02.049.Peer-Reviewed Original ResearchConceptsC-MET gene amplificationC-Met gene copy numberLiver metastasesPrimary colorectal cancerColorectal cancerGene amplificationC-MetAdvanced stage colorectal cancerAdvanced colorectal cancerStage colorectal cancerNormal colonic mucosaLiver resectionTyrosine kinaseGene copy numberDistant metastasisPrimary cancerLung cancerColonic mucosaGastric cancerNormal mucosaMetastasisNormal liverTumor growthMetastatic progressionLiver tissueGenetic variants in germline TP53 and MDM2 SNP309 are not associated with early onset colorectal cancer
Khan SA, Idrees K, Forslund A, Zeng Z, Rosenberg S, Pincas H, Barany F, Offit K, LaQuaglia MP, Paty PB. Genetic variants in germline TP53 and MDM2 SNP309 are not associated with early onset colorectal cancer. Journal Of Surgical Oncology 2008, 97: 621-625. PMID: 18381604, PMCID: PMC4381874, DOI: 10.1002/jso.20996.Peer-Reviewed Original ResearchConceptsEarly-onset colorectal cancerOnset colorectal cancerColorectal cancerMDM2 SNP309Age 30Germline variantsLi-Fraumeni kindredsP53 genePeripheral blood leukocytesNormal control populationP53 pathway genesFrequency of polymorphismsGermline TP53Blood leukocytesRare diseaseSNP309Control populationTissue availabilityPatientsConstitutional mutationsDisease susceptibilityCancerP53DiseaseGenetic variants