Dysplasia-Carcinoma Transition Specific Transcripts in Colonic Biopsy Samples 英文参考文献.docVIP

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Dysplasia-Carcinoma Transition Specific Transcripts in Colonic Biopsy Samples 英文参考文献.doc

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Dysplasia-Carcinoma Transition Specific Transcripts in Colonic Biopsy Samples 英文参考文献

Dysplasia-CarcinomaTransitionSpecificTranscriptsin ColonicBiopsySamples OrsolyaGalamb1,2.,Barnaba′sWichmann1,2*.,FerencSipos1,Sa′ndorSpisa′k1,2,TiborKrena′cs3, KingaTo′th1,KatalinLeiszter1,AlexandraKalma′r1,ZsoltTulassay1,2,Be′laMolna′r1,2 12ndDepartmentofMedicine,SemmelweisUniversity,Budapest,Hungary,2MolecularMedicineResearchUnit,HungarianAcademyofSciences,Budapest,Hungary, 31stDepartmentofPathologyandExperimentalCancerResearch,SemmelweisUniversity,Budapest,Hungary Abstract Background:Theearlymoleculardetectionofthedysplasia-carcinomatransitionmayenhancethestrengthofdiagnosisin thecaseofcolonicbiopsies.OuraimsweretoidentifycharacteristictranscriptsetsinordertodevelopdiagnosticmRNA expression patterns for objective classification of benign and malignant colorectal diseases and to test the classificatory powerofthesemarkersonanindependentsampleset. Methodology/Principal Findings: Colorectal cancer (CRC) and adenoma specific transcript sets were identified using HGU133plus2microarraysand53biopsies(22CRC,20adenomaand11normal).Ninety-fourindependentbiopsies(27CRC, 29adenomaand38normal)wereanalyzedonmicroarraysfortestingtheclassificatorypowerofthediscriminatorygenes. Array real-time PCR validation was done on 68 independent samples (24 CRC, 24 adenoma and 20 normal). A set of 11 transcripts(includingCXCL1,CHI3L1andGREM1)wasdeterminedwhichcouldcorrectlydiscriminatebetweenhigh-grade dysplasticadenomaandCRCsamplesby100%sensitivityand88.9%specificity.Thediscriminatorypowerofthemarkerset wasprovedtobehighonindependentsamplesinbothmicroarrayandRT-PCRanalyses.95.6%oforiginaland94.1%of cross-validatedsampleswascorrectlyclassifiedindiscriminantanalysis. Conclusions/Significance: The identified transcripts could correctly characterize the dysplasia-carcinoma transition in biopsysamples,alsoonalargeindependentsampleset.Thesemarkerscanestablishthebasisofgeneexpressionbased diagnosticclassificationofcolorectalcancer.DiagnosticRT-PCRcardscanbecomepartoftheautomatedroutineprocedure.