Selection of a novel drug-response predictor in esophageal cancer: A novel screening method using microarray and identification of IFITM1 as a potent marker gene of CDDP response

作者: Shoichi Fumoto , Tatsushi Shimokuni , Keiji Tanimoto , Keiko Hiyama , Keiko Otani

DOI: 10.3892/IJO.32.2.413

关键词: Gene expression profilingGeneticsGene expressionBiomarker (medicine)CancerBiologyMicroarrayPersonalized medicineGenetic markerCancer researchMarker gene

摘要: Prior laboratory prediction of individual drug response is key importance in esophageal squamous cell carcinoma (ESCC), because the extremely narrow therapeutic index chemotherapy. However, very few critical markers have been validated to date for ESCC. We previously demonstrated that simultaneous performance two different types comprehensive gene expression analysis might provide a way identify potent marker genes sensitivity from expression-sensitivity correlation alone, but screening method appeared not be always effective. Therefore, we attempted novel using new statistical oligonucleotide microarray data, based on two-dimensional mixed normal model, and selected 3 7 candidates 5-fluorouracil (5-FU) cis-platinum (CDDP), respectively. Interferon induced transmembrane protein 1 (IFITM1) being suggested as Wnt pathway, was commonly both methods. The transfection analyses siRNA-mediated knock-down experiments revealed IFITM1 closely related cellular CDDP. Considering fact determined by multiple genes, established best linear model quantified data set all including IFITM1, which converted ESCC lines into an IC50 value each drug. In same way, representative vitro, developed highly predictive formulae disease-free survival (DFS) CDDP/5-FU combination after curative operation cancer patients (R=0.917). A can powerful tool drug-response determinants, biomarker CDDP

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