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
Discovery 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 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 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 patients
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 association
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 mutationsPalliative 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
2019
Hepatocellular carcinoma: Impact of academic setting and hospital volume on patient survival
Uhlig J, Sellers CM, Khan SA, Cha C, Kim HS. Hepatocellular carcinoma: Impact of academic setting and hospital volume on patient survival. Surgical Oncology 2019, 31: 111-118. PMID: 31654956, DOI: 10.1016/j.suronc.2019.10.009.Peer-Reviewed Original ResearchMeSH KeywordsAcademic Medical CentersAntineoplastic Combined Chemotherapy ProtocolsCarcinoma, HepatocellularCombined Modality TherapyDatabases, FactualFemaleFollow-Up StudiesHepatectomyHospitals, High-VolumeHospitals, Low-VolumeHumansLiver NeoplasmsLiver TransplantationMaleMiddle AgedPractice Patterns, Physicians'PrognosisRetrospective StudiesSurvival RateConceptsOverall survivalHepatocellular carcinomaAcademic centersHospital volumePatient survivalInterventional oncologyYoung African American patientsHigh-volume academic centersMultivariable Cox regressionFirst-line treatmentLow-volume centersLonger patient survivalAfrican American patientsHCC treatment modalitiesNon-academic centersLiver transplantMultivariable adjustmentPatient demographicsSurgical resectionLine treatmentCox regressionPotential confoundersVolume centersTreatment modalitiesAmerican patientsDigital Inference of Immune Microenvironment Reveals Low-Risk Subtype of Early Lung Adenocarcinoma
Kurbatov V, Balayev A, Saffarzadeh A, Heller DR, Boffa DJ, Blasberg JD, Lu J, Khan SA. Digital Inference of Immune Microenvironment Reveals Low-Risk Subtype of Early Lung Adenocarcinoma. The Annals Of Thoracic Surgery 2019, 109: 343-349. PMID: 31568747, DOI: 10.1016/j.athoracsur.2019.08.050.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinoma of LungAdultAgedCohort StudiesDatabases, FactualDisease-Free SurvivalFemaleHumansImmunotherapyKaplan-Meier EstimateLung NeoplasmsMaleMiddle AgedNeoplasm InvasivenessNeoplasm StagingPneumonectomyPrognosisProportional Hazards ModelsRetrospective StudiesRisk AssessmentSurvival AnalysisTumor MicroenvironmentConceptsTumor immune microenvironmentImmune microenvironmentLung adenocarcinomaOverall survivalRisk groupsMast cellsCox proportional hazard modelingEarly-stage lung adenocarcinomaLow-risk subtypesKaplan-Meier analysisPathological staging systemProportional hazard modelingImproved clinical outcomesCancer immune microenvironmentImmune cell typesEarly lung adenocarcinomaActivation stateClinical outcomesValidation cohortMacrophage contentStaging systemMultivariable modelCIBERSORT analysisPatientsClinical decisionPatterns of failure after immunotherapy with checkpoint inhibitors predict durable progression-free survival after local therapy for metastatic melanoma
Klemen ND, Wang M, Feingold PL, Cooper K, Pavri SN, Han D, Detterbeck FC, Boffa DJ, Khan SA, Olino K, Clune J, Ariyan S, Salem RR, Weiss SA, Kluger HM, Sznol M, Cha C. Patterns of failure after immunotherapy with checkpoint inhibitors predict durable progression-free survival after local therapy for metastatic melanoma. Journal For ImmunoTherapy Of Cancer 2019, 7: 196. PMID: 31340861, PMCID: PMC6657062, DOI: 10.1186/s40425-019-0672-3.Peer-Reviewed Original ResearchConceptsThree-year progression-free survivalProgression-free survivalDisease-specific survivalFive-year disease-specific survivalPatterns of failureDurable progression-free survivalLocal therapyStereotactic body radiotherapyMetastatic melanomaNew metastasesPatient selectionIndependent radiological reviewOngoing complete responseResultsFour hundred twentyEvidence of diseaseCNS metastasisCPI treatmentImmunotherapy failureCheckpoint inhibitorsMost patientsProgressive diseaseRadiological reviewComplete responsePD-1PD-L1The Role of Bowel Preparation in Open, Minimally Invasive, and Converted-to-Open Colectomy
Luo J, Liu Z, Pei KY, Khan SA, Wang X, Yang M, Wang X, Zhang Y. The Role of Bowel Preparation in Open, Minimally Invasive, and Converted-to-Open Colectomy. Journal Of Surgical Research 2019, 242: 183-192. PMID: 31085366, DOI: 10.1016/j.jss.2019.02.039.Peer-Reviewed Original ResearchMeSH KeywordsAdministration, OralAgedAged, 80 and overAnti-Bacterial AgentsAntibiotic ProphylaxisCatharticsColectomyColonic DiseasesConversion to Open SurgeryElective Surgical ProceduresFemaleHospital MortalityHumansLaparoscopyLength of StayMaleMiddle AgedPostoperative ComplicationsPreoperative CareRetrospective StudiesRobotic Surgical ProceduresConceptsAntibiotic bowel preparationMechanical bowel preparationBowel preparationProtective effectElective colectomyPostoperative complicationsMajor complicationsReduced riskMultivariate logistic regression modelLength of stayStrong protective effectLogistic regression modelsStudy time periodInfectious complicationsAnastomotic leakOpen colectomyPreoperative strategyInvasive colectomyOpen groupColectomyAmerican CollegeComplicationsPatientsOverall populationRobotic surgeryPractice Patterns and Guideline Non-Adherence in Surgical Management of Appendiceal Carcinoid Tumors
Heller DR, Jean RA, Luo J, Kurbatov V, Grisotti G, Jacobs D, Chiu AS, Zhang Y, Khan SA. Practice Patterns and Guideline Non-Adherence in Surgical Management of Appendiceal Carcinoid Tumors. Journal Of The American College Of Surgeons 2019, 228: 839-851. PMID: 30898583, PMCID: PMC6751559, DOI: 10.1016/j.jamcollsurg.2019.02.050.Peer-Reviewed Original ResearchConceptsNational Comprehensive Cancer Network guidelinesAge 65 yearsAppendiceal carcinoid tumorsAppendiceal carcinoidsLarge tumorsPractice patternsOverall survivalCarcinoid tumorsSurgical managementNetwork guidelinesProcedure typeSmall tumorsHistory of malignancyNational Cancer DatabaseNational practice patternsMultivariable logistic regressionImpact of guidelinesCox proportional hazardsAggressive resectionLymphovascular invasionClinical factorsTreatment guidelinesTumor sizePatient groupNon-AdherenceDoes sentinel lymph node status have prognostic significance in patients with acral lentiginous melanoma?
Pavri SN, Han G, Khan S, Han D. Does sentinel lymph node status have prognostic significance in patients with acral lentiginous melanoma? Journal Of Surgical Oncology 2019, 119: 1060-1069. PMID: 30883783, DOI: 10.1002/jso.25445.Peer-Reviewed Original ResearchConceptsSentinel lymph node biopsyMelanoma-specific survivalAcral lentiginous melanomaSLN metastasisOverall survivalPositive SLNMultivariable analysisLentiginous melanomaALM casesSentinel lymph node statusClark level IVLymph node biopsyLymph node statusWorse overall survivalSignificant prognostic informationSLNB statusUlceration statusNegative SLNStudy patientsNode biopsyPrognostic benefitSEER databaseSLN statusMedian ageClinicopathological factorsIntrahepatic Cholangiocarcinoma: Socioeconomic Discrepancies, Contemporary Treatment Approaches and Survival Trends from the National Cancer Database
Uhlig J, Sellers CM, Cha C, Khan SA, Lacy J, Stein SM, Kim HS. Intrahepatic Cholangiocarcinoma: Socioeconomic Discrepancies, Contemporary Treatment Approaches and Survival Trends from the National Cancer Database. Annals Of Surgical Oncology 2019, 26: 1993-2000. PMID: 30693451, DOI: 10.1245/s10434-019-07175-4.Peer-Reviewed Original ResearchConceptsNational Cancer DatabaseIntrahepatic cholangiocarcinomaOverall survivalMedicaid insuranceCancer DatabaseLonger survivalTreatment allocationSurvival trendsTreatment approachesInterventional oncologySocioeconomic discrepanciesHigher surgery ratesMultivariable Cox modelFirst-line treatmentCurrent treatment approachesContemporary treatment approachesLow incomeMale African AmericansEligible patientsMethodsThe 2004ICC patientsSurgery ratesMale sexTreatment predictorsCancer stage
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