Expression Profiles of the Individual Genes Corresponding to the Genes Generated by Cytotoxicity Experiments with Bortezomib in Multiple Myeloma

摘要

Objective: Multiple myeloma (MM) is currently incurable due torefractory disease relapse even under novel anti-myeloma treatment.In silico studies are effective for key decision making duringclinicopathological battles against the chronic course of MM. The aimof this present in silico study was to identify individual genes whoseexpression profiles match that of the one generated by cytotoxicityexperiments for bortezomib.Materials and Methods: We used an in silico literature miningapproach to identify potential biomarkers by creating a summarizedset of metadata derived from relevant information. The E-MTAB-783dataset containing expression data from 789 cancer cell linesincluding 8 myeloma cell lines with drug screening data from theWellcome Trust Sanger Institute database obtained from ArrayExpresswas “Robust Multi-array analysis” normalized using GeneSpringv.12.5. Drug toxicity data were obtained from the Genomics of DrugSensitivity in Cancer project. In order to identify individual geneswhose expression profiles matched that of the one generated bycytotoxicity experiments for bortezomib, we used a linear regressionbasedapproach, where we searched for statistically significantcorrelations between gene expression values and IC50 data. Theintersections of the genes were identified in 8 cell lines and used forfurther analysis.Results: Our linear regression model identified 73 genes and somegenes expression levels were found to very closely correlated withbortezomib IC50 values. When all 73 genes were used in a hierarchical cluster analysis, two major clusters of cells representing relatively sensitive and resistant cells could be identified. Pathway and molecular function analysis of all the significant genes was also investigated, as well as the genes involved in pathways. Conclusion: The findings of our present in silico study could be important not only for the understanding of the genomics of MM but also for the better arrangement of the targeted anti-myeloma therapies, such as bortezomib.