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 mapCancerTumor
2022
Evaluation 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
Palliative 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
Integrated 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
2017
Predictors of Nonadherence to NCCN Guideline Recommendations for the Management of Stage I Anal Canal Cancer.
Kole AJ, Stahl JM, Park HS, Khan SA, Johung KL. Predictors of Nonadherence to NCCN Guideline Recommendations for the Management of Stage I Anal Canal Cancer. Journal Of The National Comprehensive Cancer Network 2017, 15: 355-362. PMID: 28275036, DOI: 10.6004/jnccn.2017.0035.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntineoplastic Combined Chemotherapy ProtocolsAnus NeoplasmsCombined Modality TherapyDatabases, FactualDisease ManagementFemaleHumansMaleMedication AdherenceMiddle AgedNeoplasm GradingNeoplasm StagingOdds RatioPractice Guidelines as TopicPrognosisProportional Hazards ModelsRisk FactorsTreatment OutcomeConceptsAnal canal cancerAnal cancerNCCN recommendationsSurgical proceduresNCCN Clinical Practice GuidelinesNational Cancer Data BaseGuideline-discordant careAnal canal carcinomaPredictors of nonadherenceClinical practice guidelinesHigh tumor gradeLow-grade tumorsLogistic regression modelingNon-academic facilitiesChi-square testDefinitive chemoradiotherapyGuideline concordantConcurrent chemoradiotherapyAnal carcinomaStandard therapyClinicopathologic factorsGuideline recommendationsMultivariable analysisMale sexTumor size
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
2015
Pancreaticoduodenectomy for locally advanced colon cancer in hereditary nonpolyposis colorectal cancer
Zhu R, Grisotti G, Salem RR, Khan SA. Pancreaticoduodenectomy for locally advanced colon cancer in hereditary nonpolyposis colorectal cancer. World Journal Of Surgical Oncology 2015, 14: 12. PMID: 26769110, PMCID: PMC4714509, DOI: 10.1186/s12957-015-0755-7.Peer-Reviewed Original ResearchConceptsNonpolyposis colorectal cancerHereditary nonpolyposis colorectal cancerAdvanced colon cancerColorectal cancerColon cancerBetter long-term outcomesMulti-visceral resectionAdvanced colorectal cancerEarly-stage diseaseRare clinical entityLong-term outcomesSpecial surgical considerationsPaucity of dataAdvanced diseaseStage diseaseMultidisciplinary treatmentSubtotal colectomyPartial colectomyCase presentationWeClinical entitySurgical considerationsLynch syndromeCancerColectomyPancreaticoduodenectomy
2012
Tumor Endothelial Inflammation Predicts Clinical Outcome in Diverse Human Cancers
Pitroda SP, Zhou T, Sweis RF, Filippo M, Labay E, Beckett MA, Mauceri HJ, Liang H, Darga TE, Perakis S, Khan SA, Sutton HG, Zhang W, Khodarev NN, Garcia JG, Weichselbaum RR. Tumor Endothelial Inflammation Predicts Clinical Outcome in Diverse Human Cancers. PLOS ONE 2012, 7: e46104. PMID: 23056240, PMCID: PMC3464251, DOI: 10.1371/journal.pone.0046104.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAnimalsBreast NeoplasmsCell Line, TumorCells, CulturedColonic NeoplasmsEndothelial CellsEndothelium, VascularFemaleGene Expression ProfilingGliomaHuman Umbilical Vein Endothelial CellsHumansInflammationKaplan-Meier EstimateLung NeoplasmsMaleMiceMiddle AgedMultivariate AnalysisNeoplasmsNeovascularization, PathologicOligonucleotide Array Sequence AnalysisTumor Necrosis Factor-alphaConceptsEndothelial inflammationEndothelial cellsOverall survivalHuman cancersDiverse human cancersExperimental modelTumor-associated endothelial cellsStromal inflammatory responsePathological prognostic factorsEndothelial-derived factorsPro-inflammatory cytokinesInflammatory gene expressionPathologic tissue specimensUntreated endothelial cellsVascular endothelial cellsMultiple human cancersInflammatory signatureHuman endothelial cellsPrognostic factorsClinical outcomesChronic inflammationInflammatory pathwaysLung cancerTumor necrosisInflammatory response
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 loss