2023
Utility of promoter hypermethylation in malignant risk stratification of intraductal papillary mucinous neoplasms
Chhoda A, Sharma A, Sailo B, Tang H, Ruzgar N, Tan W, Ying L, Khatri R, Narayanan A, Mane S, De Kumar B, Wood L, Iacobuzio-Donahue C, Wolfgang C, Kunstman J, Salem R, Farrell J, Ahuja N. Utility of promoter hypermethylation in malignant risk stratification of intraductal papillary mucinous neoplasms. Clinical Epigenetics 2023, 15: 28. PMID: 36803844, PMCID: PMC9942382, DOI: 10.1186/s13148-023-01429-5.Peer-Reviewed Original ResearchConceptsPapillary mucinous neoplasmMalignant risk stratificationCACNA1G geneRisk stratificationMucinous neoplasmsBiomarker panelBackgroundIntraductal papillary mucinous neoplasmIntraductal papillary mucinous neoplasmEarly detectionPrevious case-control studyHigh-grade dysplasiaCase-control studyPancreatic cancer precursorsReceiver Operating Characteristic (ROC) curve analysisSignificant diagnostic challengeCross-sectional imagingCharacteristic curve analysisOperating Characteristic curve analysisG geneHigh diagnostic specificityPrior validation studiesSignificant procedural riskIPMN tissuesSurgical resectionAdvanced neoplasia
2019
Promoter methylation of ADAMTS1 and BNC1 as potential biomarkers for early detection of pancreatic cancer in blood
Eissa MAL, Lerner L, Abdelfatah E, Shankar N, Canner JK, Hasan NM, Yaghoobi V, Huang B, Kerner Z, Takaesu F, Wolfgang C, Kwak R, Ruiz M, Tam M, Pisanic TR, Iacobuzio-Donahue CA, Hruban RH, He J, Wang TH, Wood LD, Sharma A, Ahuja N. Promoter methylation of ADAMTS1 and BNC1 as potential biomarkers for early detection of pancreatic cancer in blood. Clinical Epigenetics 2019, 11: 59. PMID: 30953539, PMCID: PMC6451253, DOI: 10.1186/s13148-019-0650-0.Peer-Reviewed Original ResearchConceptsStage IIB diseasePancreatic cancerIIB diseaseStage IIACA 19Stage IBiomarker panelBlood-based biomarker panelPre-operative CA 19Stage I patientsCell-free tumor DNAHigh-risk populationPotential blood biomarkersMost pancreatic cancersBackgroundDespite improvementsCurative resectionSurgical resectionI patientsTwo-gene panelPancreas cancerBlood biomarkersCurative potentialCancer managementAdvanced stageCombination panel
2018
Genomics of Peritoneal Malignancies
Karunasena E, Sham J, McMahon KW, Ahuja N. Genomics of Peritoneal Malignancies. Surgical Oncology Clinics Of North America 2018, 27: 463-475. PMID: 29935683, DOI: 10.1016/j.soc.2018.02.004.Peer-Reviewed Original ResearchConceptsPeritoneal malignancyPeritoneal metastasisSimilar genetic mutationsEpithelial-mesenchymal transitionBiologic therapySurgical resectionMetastatic lesionsPredictive markerPrimary tumorIntraabdominal organsAggressive cancerMultiple cancersMetastasisMalignancyGenetic mutationsCancerOrgansResectionChemotherapyPeritoneumTherapyLesionsTumorsAbdomenAdjunct
2017
The Roles of DNA Methylation in the Stages of Cancer
McMahon KW, Karunasena E, Ahuja N. The Roles of DNA Methylation in the Stages of Cancer. The Cancer Journal 2017, 23: 257-261. PMID: 28926425, PMCID: PMC5657558, DOI: 10.1097/ppo.0000000000000279.Peer-Reviewed Original ResearchNeutrophil-to-lymphocyte Ratio is a Predictive Marker for Invasive Malignancy in Intraductal Papillary Mucinous Neoplasms of the Pancreas
Gemenetzis G, Bagante F, Griffin JF, Rezaee N, Javed AA, Manos LL, Lennon AM, Wood LD, Hruban RH, Zheng L, Zaheer A, Fishman EK, Ahuja N, Cameron JL, Weiss MJ, He J, Wolfgang CL. Neutrophil-to-lymphocyte Ratio is a Predictive Marker for Invasive Malignancy in Intraductal Papillary Mucinous Neoplasms of the Pancreas. Annals Of Surgery 2017, 266: 339-345. PMID: 27631774, DOI: 10.1097/sla.0000000000001988.Peer-Reviewed Original ResearchConceptsIntraductal papillary mucinous neoplasmPapillary mucinous neoplasmInvasive carcinomaPredictive nomogramLymphocyte ratioMucinous neoplasmsInvasive malignancyPredictive markerMain pancreatic duct dilatationEnhanced solid componentLymphocyte ratio valuesIndependent predictive markerFurther prospective studiesPancreatic duct dilatationInflammatory markersSurgical resectionDuct dilatationNLR valuesOverall survivalProspective studyPancreatic cancerC-indexCarcinomaMultivariate analysisPatientsLong‐term survival benefit of upfront chemotherapy in patients with newly diagnosed borderline resectable pancreatic cancer
Shrestha B, Sun Y, Faisal F, Kim V, Soares K, Blair A, Herman JM, Narang A, Dholakia AS, Rosati L, Hacker‐Prietz A, Chen L, Laheru DA, De Jesus‐Acosta A, Le DT, Donehower R, Azad N, Diaz LA, Murphy A, Lee V, Fishman EK, Hruban RH, Liang T, Cameron JL, Makary M, Weiss MJ, Ahuja N, He J, Wolfgang CL, Huang C, Zheng L. Long‐term survival benefit of upfront chemotherapy in patients with newly diagnosed borderline resectable pancreatic cancer. Cancer Medicine 2017, 6: 1552-1562. PMID: 28639410, PMCID: PMC5504321, DOI: 10.1002/cam4.1104.Peer-Reviewed Original ResearchConceptsMedian overall survivalUpfront chemotherapyNeoadjuvant chemotherapyNeoadjuvant therapySurgical resectionOverall survivalUpfront chemoradiationBorderline resectable pancreatic adenocarcinomaLong-term survival benefitBorderline resectable pancreatic cancerCurative surgical resectionResectable pancreatic cancerUpfront neoadjuvant chemotherapyResectable pancreatic adenocarcinomaSubpopulation of patientsJohns Hopkins HospitalLong-term survivalCurative intentNeoadjuvant chemoradiationConsecutive patientsSurvival benefitPancreatic cancerPancreatic adenocarcinomaRetrospective analysisChemoradiationCombination Epigenetic Therapy in Advanced Breast Cancer with 5-Azacitidine and Entinostat: A Phase II National Cancer Institute/Stand Up to Cancer Study
Connolly RM, Li H, Jankowitz RC, Zhang Z, Rudek MA, Jeter SC, Slater SA, Powers P, Wolff AC, Fetting JH, Brufsky A, Piekarz R, Ahuja N, Laird PW, Shen H, Weisenberger DJ, Cope L, Herman JG, Somlo G, Garcia AA, Jones PA, Baylin SB, Davidson NE, Zahnow CA, Stearns V. Combination Epigenetic Therapy in Advanced Breast Cancer with 5-Azacitidine and Entinostat: A Phase II National Cancer Institute/Stand Up to Cancer Study. Clinical Cancer Research 2017, 23: 2691-2701. PMID: 27979916, PMCID: PMC5457329, DOI: 10.1158/1078-0432.ccr-16-1729.Peer-Reviewed Original ResearchConceptsTriple-negative breast cancerObjective response rateCombination epigenetic therapyEstrogen receptorEndocrine therapyPrimary endpointPartial responseMulticenter phase II studyEpigenetic therapyAdditional partial responsesHormone-resistant diseasePhase II studyTime of progressionBreast cancer modelClin Cancer ResHistone deacetylase inhibitorsImportant therapeutic targetPosttreatment biopsiesTNBC cohortII studyBreast cancerDNA methyltransferase inhibitorTherapeutic targetResponse rateCancer modelA Four-Gene Promoter Methylation Marker Panel Consisting of GREM1, NEURL, LAD1, and NEFH Predicts Survival of Clear Cell Renal Cell Cancer Patients
van Vlodrop IJH, Joosten SC, De Meyer T, Smits KM, Van Neste L, Melotte V, Baldewijns MMLL, Schouten LJ, van den Brandt PA, Jeschke J, Yi JM, Schuebel KE, Ahuja N, Herman JG, Aarts MJ, Bosman FT, Van Criekinge W, van Engeland M. A Four-Gene Promoter Methylation Marker Panel Consisting of GREM1, NEURL, LAD1, and NEFH Predicts Survival of Clear Cell Renal Cell Cancer Patients. Clinical Cancer Research 2017, 23: 2006-2018. PMID: 27756787, DOI: 10.1158/1078-0432.ccr-16-1236.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAutoantigensBiomarkers, TumorCarcinoma, Renal CellDisease-Free SurvivalDNA MethylationFemaleHigh-Throughput Nucleotide SequencingHumansIntercellular Signaling Peptides and ProteinsKaplan-Meier EstimateKidney NeoplasmsMaleMiddle AgedNeurofilament ProteinsNon-Fibrillar CollagensOligonucleotide Array Sequence AnalysisPrognosisPromoter Regions, GeneticProportional Hazards ModelsUbiquitin-Protein LigasesConceptsClear cell renal cell carcinomaPrognostic modelNonmetastatic clear cell renal cell carcinomaMethylation markersCox proportional hazards modelPrimary clear cell renal cell carcinomaIndependent patient seriesCause-specific survivalOutcomes of patientsCell renal cell carcinomaPrognosis of patientsKaplan-Meier curvesLog-rank testConfidence intervalsCurrent prognostic modelsRenal cell carcinomaProportional hazards modelClin Cancer ResCcRCC cell linesCancer Genome AtlasClinicopathologic featuresPatient seriesCell carcinomaMethylation-specific PCRPoor survival
2016
Circulating Tumor Cell Phenotype Predicts Recurrence and Survival in Pancreatic Adenocarcinoma
Poruk KE, Valero V, Saunders T, Blackford AL, Griffin JF, Poling J, Hruban RH, Anders RA, Herman J, Zheng L, Rasheed ZA, Laheru DA, Ahuja N, Weiss MJ, Cameron JL, Goggins M, Iacobuzio-Donahue CA, Wood LD, Wolfgang CL. Circulating Tumor Cell Phenotype Predicts Recurrence and Survival in Pancreatic Adenocarcinoma. Annals Of Surgery 2016, 264: 1073-1081. PMID: 26756760, PMCID: PMC4936958, DOI: 10.1097/sla.0000000000001600.Peer-Reviewed Original ResearchConceptsCytokeratin-positive CTCsPancreatic adenocarcinomaMesenchymal markersVimentin-positive CTCsEpithelial tumor cells (ISET) methodFourth leading causeBetter treatment stratificationPortal blood samplesSignificant independent predictorsPotential prognostic biomarkerBiology of metastasisDetection of CTCsSurgical resectionIndependent predictorsPrognostic factorsMedian timeMultivariable analysisPDAC patientsPrognostic utilityCancer deathPatient prognosisLeading causeTreatment stratificationCancer recurrencePoor survivalIGFBP-3 Gene Methylation in Primary Tumor Predicts Recurrence of Stage II Colorectal Cancers
Fu T, Pappou EP, Guzzetta AA, de Freitas Calmon M, Sun L, Herrera A, Li F, Wolfgang CL, Baylin SB, Iacobuzio-Donahue CA, Tong W, Ahuja N. IGFBP-3 Gene Methylation in Primary Tumor Predicts Recurrence of Stage II Colorectal Cancers. Annals Of Surgery 2016, 263: 337-344. PMID: 25822686, PMCID: PMC4648704, DOI: 10.1097/sla.0000000000001204.Peer-Reviewed Original ResearchConceptsStage II colorectal cancerRisk of recurrenceIGFBP-3 methylationLymph nodesColorectal cancerHazard ratioPrimary tumorHigh riskIndependent cohortFive-year recurrence-free survival ratesRecurrence-free survival ratesHigh-risk patientsSignificant prognostic factorsIdentification of patientsProportional hazards modelIGFBP-3Prognostic factorsTumor characteristicsPredicts RecurrenceHazards modelPatientsRecurrenceSurvival rateMultivariate analysisSurgery
2015
A Combination of Molecular Markers and Clinical Features Improve the Classification of Pancreatic Cysts
Springer S, Wang Y, Dal Molin M, Masica DL, Jiao Y, Kinde I, Blackford A, Raman SP, Wolfgang CL, Tomita T, Niknafs N, Douville C, Ptak J, Dobbyn L, Allen PJ, Klimstra DS, Schattner MA, Schmidt CM, Yip-Schneider M, Cummings OW, Brand RE, Zeh HJ, Singhi AD, Scarpa A, Salvia R, Malleo G, Zamboni G, Falconi M, Jang JY, Kim SW, Kwon W, Hong SM, Song KB, Kim SC, Swan N, Murphy J, Geoghegan J, Brugge W, Castillo C, Mino-Kenudson M, Schulick R, Edil BH, Adsay V, Paulino J, van Hooft J, Yachida S, Nara S, Hiraoka N, Yamao K, Hijioka S, van der Merwe S, Goggins M, Canto MI, Ahuja N, Hirose K, Makary M, Weiss MJ, Cameron J, Pittman M, Eshleman JR, Diaz LA, Papadopoulos N, Kinzler KW, Karchin R, Hruban RH, Vogelstein B, Lennon AM. A Combination of Molecular Markers and Clinical Features Improve the Classification of Pancreatic Cysts. Gastroenterology 2015, 149: 1501-1510. PMID: 26253305, PMCID: PMC4782782, DOI: 10.1053/j.gastro.2015.07.041.Peer-Reviewed Original ResearchPromoter Methylation of CDO1 Identifies Clear-Cell Renal Cell Cancer Patients with Poor Survival Outcome
Deckers IA, Schouten LJ, Van Neste L, van Vlodrop IJ, Soetekouw PM, Baldewijns MM, Jeschke J, Ahuja N, Herman JG, van den Brandt PA, van Engeland M. Promoter Methylation of CDO1 Identifies Clear-Cell Renal Cell Cancer Patients with Poor Survival Outcome. Clinical Cancer Research 2015, 21: 3492-3500. PMID: 25904753, PMCID: PMC4612631, DOI: 10.1158/1078-0432.ccr-14-2049.Peer-Reviewed Original ResearchConceptsCDO1 promoter methylationNetherlands Cohort StudyCysteine dioxygenase type 1Prognostic markerPromoter methylationCcRCC casesRenal cell cancer patientsProspective Netherlands Cohort StudyMultivariate modelRelative prognostic valueKaplan-Meier curvesPopulation-based seriesClear cell renal cell cancer (ccRCC) patientsCurrent prognostic markersPoor survival outcomesConfidence intervalsRelevant prognostic informationIndividual patient outcomesMultivariate HRCohort studyMethylation-specific PCR analysisCancer Genome AtlasPrognostic factorsPrognostic valuePromoter methylation statusPersonalized Approaches to Gastrointestinal Cancers Importance of Integrating Genomic Information to Guide Therapy
He J, Ahuja N. Personalized Approaches to Gastrointestinal Cancers Importance of Integrating Genomic Information to Guide Therapy. Surgical Clinics Of North America 2015, 95: 1081-1094. PMID: 26315525, DOI: 10.1016/j.suc.2015.05.002.Peer-Reviewed Original ResearchConceptsGenetic testingPersonalized approachHigh-risk family membersCancer prevention strategiesComplex tumor heterogeneityTherapeutic decision makingProphylactic surgeryClinical trialsPrevention strategiesCancer behaviorGermline mutationsSuch personalized approachesTumor heterogeneityPatientsTherapyFamily membersBiopsySurgeryCancerCliniciansDifferent groupsTrialsSpectrin Repeat Containing Nuclear Envelope 1 and Forkhead Box Protein E1 Are Promising Markers for the Detection of Colorectal Cancer in Blood
Melotte V, Yi JM, Lentjes MH, Smits KM, Van Neste L, Niessen HE, Wouters KA, Louwagie J, Schuebel KE, Herman JG, Baylin SB, van Criekinge W, Meijer GA, Ahuja N, van Engeland M. Spectrin Repeat Containing Nuclear Envelope 1 and Forkhead Box Protein E1 Are Promising Markers for the Detection of Colorectal Cancer in Blood. Cancer Prevention Research 2015, 8: 157-164. PMID: 25538088, PMCID: PMC4316751, DOI: 10.1158/1940-6207.capr-14-0198.Peer-Reviewed Original ResearchAgedArea Under CurveBiomarkers, TumorCell Line, TumorColorectal NeoplasmsCytoskeletal ProteinsDNA MethylationFemaleForkhead Transcription FactorsHumansMaleMiddle AgedNerve Tissue ProteinsNuclear ProteinsPromoter Regions, GeneticReal-Time Polymerase Chain ReactionROC CurveSensitivity and SpecificityTransfection
2014
The promise of methylation on beads for cancer detection and treatment
Guzzetta AA, Pisanic T, Sharma P, Yi JM, Stark A, Wang TH, Ahuja N. The promise of methylation on beads for cancer detection and treatment. Expert Review Of Molecular Diagnostics 2014, 14: 845-852. PMID: 25136840, PMCID: PMC4427839, DOI: 10.1586/14737159.2014.943665.Peer-Reviewed Original ResearchFunctional Identification of Cancer-Specific Methylation of CDO1, HOXA9, and TAC1 for the Diagnosis of Lung Cancer
Wrangle J, Machida EO, Danilova L, Hulbert A, Franco N, Zhang W, Glöckner SC, Tessema M, Van Neste L, Easwaran H, Schuebel KE, Licchesi J, Hooker CM, Ahuja N, Amano J, Belinsky SA, Baylin SB, Herman JG, Brock MV. Functional Identification of Cancer-Specific Methylation of CDO1, HOXA9, and TAC1 for the Diagnosis of Lung Cancer. Clinical Cancer Research 2014, 20: 1856-1864. PMID: 24486589, PMCID: PMC4019442, DOI: 10.1158/1078-0432.ccr-13-2109.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerThree-gene panelLung cancerIndependent cohortPrimary NSCLC samplesCell lung cancerNSCLC cell linesNovel diagnostic biomarkersAdjuvant chemotherapyMolecular diagnostic testsCancer Genome AtlasCancer mortalityCancer-specific methylationSurgical specimensNSCLC samplesMolecular stagingEarly diagnosisDiagnostic biomarkersNormal tissuesDiagnostic testsCohortCancerGenome AtlasMethylation biomarkersCell lines
2013
Novel Methylation Biomarker Panel for the Early Detection of Pancreatic Cancer
Yi JM, Guzzetta AA, Bailey VJ, Downing SR, Van Neste L, Chiappinelli KB, Keeley BP, Stark A, Herrera A, Wolfgang C, Pappou EP, Iacobuzio-Donahue CA, Goggins MG, Herman JG, Wang TH, Baylin SB, Ahuja N. Novel Methylation Biomarker Panel for the Early Detection of Pancreatic Cancer. Clinical Cancer Research 2013, 19: 6544-6555. PMID: 24088737, PMCID: PMC4310572, DOI: 10.1158/1078-0432.ccr-12-3224.Peer-Reviewed Original ResearchADAM ProteinsADAMTS1 ProteinBiomarkers, TumorCarcinoma in SituCell Line, TumorCell MovementCell ProliferationCpG IslandsDNADNA MethylationDNA-Binding ProteinsEarly Detection of CancerEpigenesis, GeneticFemaleGene Expression ProfilingGene Expression Regulation, NeoplasticHumansMaleMolecular Diagnostic TechniquesPancreatic NeoplasmsPromoter Regions, GeneticProportional Hazards ModelsSensitivity and SpecificitySequence Analysis, DNATranscription FactorsTranscriptomeExtrathoracic Location and “Borderline” Histology are Associated with Recurrence of Solitary Fibrous Tumors After Surgical Resection
Wilky BA, Montgomery EA, Guzzetta AA, Ahuja N, Meyer CF. Extrathoracic Location and “Borderline” Histology are Associated with Recurrence of Solitary Fibrous Tumors After Surgical Resection. Annals Of Surgical Oncology 2013, 20: 4080-4089. PMID: 24046107, PMCID: PMC4124630, DOI: 10.1245/s10434-013-3241-x.Peer-Reviewed Original ResearchConceptsExtrathoracic solitary fibrous tumorsBenign solitary fibrous tumorSolitary fibrous tumorMalignant histologyExtrathoracic locationPathologic criteriaFibrous tumorMetastatic solitary fibrous tumorPatient pathology reportsKaplan-Meier methodPredictors of recurrencePrimary care physiciansHead/neckSurgical pathology databaseMethodsWith IRB approvalSFTS patientsSurgical resectionComplete resectionCare physiciansWorse prognosisIntraabdominal sitesPathology databaseMedical recordsPathology reportsPatient historyExtraction and processing of circulating DNA from large sample volumes using methylation on beads for the detection of rare epigenetic events
Keeley B, Stark A, Pisanic TR, Kwak R, Zhang Y, Wrangle J, Baylin S, Herman J, Ahuja N, Brock MV, Wang TH. Extraction and processing of circulating DNA from large sample volumes using methylation on beads for the detection of rare epigenetic events. Clinica Chimica Acta 2013, 425: 169-175. PMID: 23911908, PMCID: PMC3963364, DOI: 10.1016/j.cca.2013.07.023.Peer-Reviewed Original ResearchKRAS G>A mutation favors poor tumor differentiation but may not be associated with prognosis in patients with curatively resected duodenal adenocarcinoma
Fu T, Guzzetta AA, Jeschke J, Vatapalli R, Dave P, Hooker CM, Morgan R, Iacobuzio‐Donahue C, Liu B, Ahuja N. KRAS G>A mutation favors poor tumor differentiation but may not be associated with prognosis in patients with curatively resected duodenal adenocarcinoma. International Journal Of Cancer 2013, 132: 2502-2509. PMID: 23065691, PMCID: PMC3579006, DOI: 10.1002/ijc.27910.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaBiomarkers, TumorCell DifferentiationDNA, NeoplasmDuodenal NeoplasmsFemaleHumansMaleMicrosatellite RepeatsMiddle AgedMutationNeoplasm Recurrence, LocalNeoplasm StagingPolymerase Chain ReactionPrognosisProto-Oncogene ProteinsProto-Oncogene Proteins p21(ras)Ras ProteinsSurvival RateConceptsPoor tumor differentiationKRAS GPositive lymph nodesDuodenal adenocarcinomaKRAS mutationsTumor differentiationMutation carriersDistant relapseLymph nodesMultivariate logistic regression analysisShorter relapse-free survivalFuture staging systemsRelapse-free survivalShorter overall survivalPossible prognostic roleLogistic regression analysisCurative resectionPoor OSOverall survivalPrognostic roleTumor characteristicsClinical outcomesClinicopathological characteristicsPoor prognosisPrognostic significance