Featured Publications
Low Programmed Death-Ligand 1–Expressing Subgroup Outcomes of First-Line Immune Checkpoint Inhibitors in Gastric or Esophageal Adenocarcinoma
Zhao J, Yap D, Chan Y, Tan B, Teo C, Syn N, Smyth E, Soon Y, Sundar R. Low Programmed Death-Ligand 1–Expressing Subgroup Outcomes of First-Line Immune Checkpoint Inhibitors in Gastric or Esophageal Adenocarcinoma. Journal Of Clinical Oncology 2021, 40: 392-402. PMID: 34860570, DOI: 10.1200/jco.21.01862.Peer-Reviewed Original ResearchConceptsProgrammed death-ligand 1Combined positive scoreImmune checkpoint inhibitorsKEYNOTE-062First-line treatmentCheckMate-649Checkpoint inhibitorsEsophageal adenocarcinomaKaplan-MeierEstimate time-to-event outcomesFirst-line immune checkpoint inhibitorsPD-L1 combined positive scoreProgrammed death ligand 1 subgroupsPatients treated with pembrolizumabPD-L1-expressing tumorsRandomized phase III trialEfficacy of ICIsPD-L1 subgroupsProgression-free survivalDeath-ligand 1Phase III trialsUS Food and Drug AdministrationPrimary manuscriptsFood and Drug AdministrationCPS-1Machine-learning model derived gene signature predictive of paclitaxel survival benefit in gastric cancer: results from the randomised phase III SAMIT trial
Sundar R, Kumarakulasinghe N, Chan Y, Yoshida K, Yoshikawa T, Miyagi Y, Rino Y, Masuda M, Guan J, Sakamoto J, Tanaka S, Tan A, Hoppe M, Jeyasekharan A, Ng C, De Simone M, Grabsch H, Lee J, Oshima T, Tsuburaya A, Tan P. Machine-learning model derived gene signature predictive of paclitaxel survival benefit in gastric cancer: results from the randomised phase III SAMIT trial. Gut 2021, 71: 676-685. PMID: 33980610, PMCID: PMC8921574, DOI: 10.1136/gutjnl-2021-324060.Peer-Reviewed Original ResearchConceptsDisease free survivalValidation cohortGastric cancerGene signatureSurvival benefitPac-SensitiveNo survival differenceSelection of patientsGC trialsFree survivalPaclitaxel chemotherapyCurative surgeryMetastatic patientsPredictive biomarkersTraining cohortSurvival differencesIndependent cohortNanoString panelGC patientsPaclitaxelPatientsNanoString profilingCohortGroup trialUFTSpatial profiling of gastric cancer patient-matched primary and locoregional metastases reveals principles of tumour dissemination
Sundar R, Liu D, Hutchins G, Slaney H, Silva A, Oosting J, Hayden J, Hewitt L, Ng C, Mangalvedhekar A, Ng S, Tan I, Tan P, Grabsch H. Spatial profiling of gastric cancer patient-matched primary and locoregional metastases reveals principles of tumour dissemination. Gut 2020, 70: 1823-1832. PMID: 33229445, PMCID: PMC8458060, DOI: 10.1136/gutjnl-2020-320805.Peer-Reviewed Original ResearchConceptsPrimary gastric cancerLymph node metastasisPrimary tumorGastric cancerIntratumour heterogeneityNode metastasisMatched lymph node metastasesRegional lymph node metastasisMultiplex ligation-dependent probe amplificationLigation-dependent probe amplificationPatient-matchedProgressive genomic changesDNA copy number profilesEndoscopic mucosal biopsiesCopy number profilesTherapeutically relevant genesLocoregional metastasesTumor disseminationResected samplesTargeted therapyHistomorphological phenotypesProbe amplificationBiomarker testingClinical trialsNanoString results
2022
Pan-cancer pervasive upregulation of 3′ UTR splicing drives tumourigenesis
Chan J, Zhang B, Chew X, Salhi A, Kwok Z, Lim C, Desi N, Subramaniam N, Siemens A, Kinanti T, Ong S, Sanchez-Mejias A, Ly P, An O, Sundar R, Fan X, Wang S, Siew B, Lee K, Chong C, Lieske B, Cheong W, Goh Y, Fam W, Ooi M, Koh B, Iyer S, Ling W, Chen J, Yoong B, Chanwat R, Bonney G, Goh B, Zhai W, Fullwood M, Wang W, Tan K, Chng W, Dan Y, Pitt J, Roca X, Guccione E, Vardy L, Chen L, Gao X, Chow P, Yang H, Tay Y. Pan-cancer pervasive upregulation of 3′ UTR splicing drives tumourigenesis. Nature Cell Biology 2022, 24: 928-939. PMID: 35618746, PMCID: PMC9203280, DOI: 10.1038/s41556-022-00913-z.Peer-Reviewed Original ResearchMeSH Keywords3' Untranslated RegionsAdenocarcinomaAlternative SplicingAnimalsCarcinogenesisColonic NeoplasmsMammalsUp-RegulationConceptsUntranslated regionProtein-coding alterationsPost-transcriptional regulationAnti-cancer therapeuticsMammalian genesAlternative polyadenylationPan-cancer landscapeSplicing studiesAntisense oligonucleotide-mediated inhibitionUTR variantsDysregulation eventsSplicingOncogenic functionActivated oncogenesOncogene expressionMessenger RNAOncogeneTumor progressionPolyadenylationPoor prognosisHepatocellular carcinomaUpregulationColon adenocarcinomaGenesRNA
2021
Small bowel adenocarcinoma in Crohn’s disease: a systematic review and meta-analysis of the prevalence, manifestation, histopathology, and outcomes
Chin Y, Jain S, Lee M, Ng C, Lin S, Mai A, Muthiah M, Foo F, Sundar R, Ong D, Leow W, Leong R, Chan W. Small bowel adenocarcinoma in Crohn’s disease: a systematic review and meta-analysis of the prevalence, manifestation, histopathology, and outcomes. International Journal Of Colorectal Disease 2021, 37: 239-250. PMID: 34704127, DOI: 10.1007/s00384-021-04050-1.Peer-Reviewed Original ResearchConceptsMolecular analysis findingsCrohn's diseaseOverall survivalClinical presentationBowel adenocarcinomaCD patientsInflammatory bowel disease patientsMeta-analysisSmall bowel adenocarcinomaAssociated with Crohn's diseaseConclusionOur meta-analysisMethodsElectronic databases MedlineStatistically significant increaseEpithelial dysplasiaAbdominal painMismatch repair deficiencyKRAS mutationsRadiological featuresHistopathological findingsGenetic mutationsPatientsRepair deficiencyResultsIn totalDisease patientsHistopathology“3G” Trial: An RNA Editing Signature to Guide Gastric Cancer ChemotherapyRNA Editing Signature in Gastric Cancer
An O, Song Y, Ke X, So J, Sundar R, Yang H, Rha S, Lee M, Tay S, Ong X, Tan A, Ng M, Tantoso E, Chen L, Tan P, Yong W, Consortium S. “3G” Trial: An RNA Editing Signature to Guide Gastric Cancer ChemotherapyRNA Editing Signature in Gastric Cancer. Cancer Research 2021, 81: 2788-2798. PMID: 33558338, DOI: 10.1158/0008-5472.can-20-2872.Peer-Reviewed Original ResearchConceptsAdvanced gastric cancerRNA editingRNA editing signaturesEditing levelsGastric cancerRNA editing eventsHigher editing levelsAdenosine-to-inosineRNA editing analysisGastric cancer cell linesPredictive biomarkersStratify patientsLevels of editingGene expression profilesPredicting response to chemotherapyEditing sitesEditing eventsMolecular subtypes of gastric cancerCancer cell linesPlatinum-based chemotherapyMetastatic gastric cancerSubtypes of gastric cancerCancer Genome AtlasFirst-line therapyResponse to chemotherapy
2020
Profiling of gastric cancer cell-surface markers to achieve tumour–normal discrimination
Toh J, Hoppe M, Thakur T, Yang H, Tan K, Pang B, Ho S, Roy R, Ho K, Yeoh K, Tan P, Sundar R, Jeyasekharan A. Profiling of gastric cancer cell-surface markers to achieve tumour–normal discrimination. BMJ Open Gastroenterology 2020, 7: e000452. PMID: 32816956, PMCID: PMC7437876, DOI: 10.1136/bmjgast-2020-000452.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaAntigens, CDAntigens, Tumor-Associated, CarbohydrateCA-19-9 AntigenCarcinoembryonic AntigenCell Adhesion MoleculesClaudin-4ClaudinsEpithelial Cell Adhesion MoleculeEvaluation Studies as TopicExome SequencingGenomicsGPI-Linked ProteinsHumansImmunohistochemistryMembrane ProteinsROC CurveSensitivity and SpecificitySingaporeStomach NeoplasmsUp-RegulationConceptsWhole-transcriptome sequencingCell surface markersMultispectral immunohistochemistryPutative cell surface proteinGastric cancerNormal tissuesMatched normal samplesCA72-4Cell surface proteinsTumor tissuesLive imaging approachesAnalysis of cell surface markersMolecular profiling of cancersHighest diagnostic validityIdentification of tumor tissueTranscriptome sequencingCancer Genome AtlasProfile of cancerProtein transcriptsCancer cell surface markersCA19-9Genome AtlasDifferentiated tumorsTissue microarrayTCGA data
2019
DNA epigenetic signature predictive of benefit from neoadjuvant chemotherapy in oesophageal adenocarcinoma: results from the MRC OE02 trial
Sundar R, Ng A, Zouridis H, Padmanabhan N, Sheng T, Zhang S, Lee M, Ooi W, Qamra A, Inam I, Hewitt L, So J, Koh V, Nankivell M, Langley R, Allum W, Cunningham D, Rozen S, Yong W, Grabsch H, Tan P. DNA epigenetic signature predictive of benefit from neoadjuvant chemotherapy in oesophageal adenocarcinoma: results from the MRC OE02 trial. European Journal Of Cancer 2019, 123: 48-57. PMID: 31655359, DOI: 10.1016/j.ejca.2019.09.016.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaAdultAgedAged, 80 and overAntineoplastic Combined Chemotherapy ProtocolsCisplatinDNA MethylationEpigenesis, GeneticEsophageal NeoplasmsFemaleFluorouracilHumansMaleMiddle AgedNeoadjuvant TherapyNeoplasm GradingNeoplasm StagingPrognosisProportional Hazards ModelsRandomized Controlled Trials as TopicSurvival RateConceptsCS armNeoadjuvant chemotherapyOverall survivalOesophageal adenocarcinomaDNA methylation signaturesHistological subtypes of oesophageal cancerOesophageal cancerIndependent cohortPredictive of chemotherapy benefitSubtypes of oesophageal cancerIndependent cohort of patientsS armCox proportional hazards analysisResectable oesophageal cancerCohort of patientsPredictive of benefitMethylation signaturesDNA methylationPredictive of survivalProportional hazards analysisChemotherapy benefitHistological subtypesMetagene signatureRandomised patientsDNA methylation status
2018
Genomic Analyses and Precision Oncology in Gastroesophageal Cancer: Forwards or Backwards?
Sundar R, Tan P. Genomic Analyses and Precision Oncology in Gastroesophageal Cancer: Forwards or Backwards? Cancer Discovery 2018, 8: 14-16. PMID: 29311223, DOI: 10.1158/2159-8290.cd-17-1295.Commentaries, Editorials and Letters