Generation of a predictive melphalan resistance index by drug screen of B-cell cancer cell lines
| Autor: | Anne Bukh, Suzette Sørensen, Mette Nyegaard, Johanne Marie Holst, Hans Erik Johnsen, Steffen Falgreen, Alexander Schmitz, Karen Dybkær, Martin Boegsted, Kirsten Fogd |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
Oncology
Melphalan medicine.medical_specialty medicine.medical_treatment Science Gene Expression Antineoplastic Agents Drug resistance Biostatistics Bioinformatics Hematologic Cancers and Related Disorders Internal medicine hemic and lymphatic diseases Cell Line Tumor Cancer screening Molecular Cell Biology medicine Humans Myelomas and Lymphoproliferative Diseases Least-Squares Analysis Biology Multiple myeloma Oligonucleotide Array Sequence Analysis Chemotherapy B-Lymphocytes Multidisciplinary business.industry Gene Expression Profiling Statistics Hematology medicine.disease Lymphoma Gene expression profiling Gene Expression Regulation Neoplastic Drug Resistance Neoplasm Medicine Lymphoma Large B-Cell Diffuse Drug Screening Assays Antitumor business Multiple Myeloma Mathematics Genetic screen medicine.drug Plasmacytoma Research Article |
| Zdroj: | PLoS ONE PLoS ONE, Vol 6, Iss 4, p e19322 (2011) Bøgsted, M, Holst, J M, Fogd, K, Larsen, S F, Sørensen, S, Schmitz, A, Bukh, A, Johnsen, H E, Nyegaard, M & Dybkær, K 2011, ' Generation of a predictive melphalan resistance index by drug screen of B-cell cancer cell lines ', P L o S One, vol. 6, no. 4, pp. e19322 . https://doi.org/10.1371/journal.pone.0019322 |
| ISSN: | 1932-6203 |
| Popis: | BackgroundRecent reports indicate that in vitro drug screens combined with gene expression profiles (GEP) of cancer cell lines may generate informative signatures predicting the clinical outcome of chemotherapy. In multiple myeloma (MM) a range of new drugs have been introduced and now challenge conventional therapy including high dose melphalan. Consequently, the generation of predictive signatures for response to melphalan may have a clinical impact. The hypothesis is that melphalan screens and GEPs of B-cell cancer cell lines combined with multivariate statistics may provide predictive clinical information.Materials and methodsMicroarray based GEPs and a melphalan growth inhibition screen of 59 cancer cell lines were downloaded from the National Cancer Institute database. Equivalent data were generated for 18 B-cell cancer cell lines. Linear discriminant analyses (LDA), sparse partial least squares (SPLS) and pairwise comparisons of cell line data were used to build resistance signatures from both cell line panels. A melphalan resistance index was defined and estimated for each MM patient in a publicly available clinical data set and evaluated retrospectively by Cox proportional hazards and Kaplan-Meier survival analysis.Principal findingsBoth cell line panels performed well with respect to internal validation of the SPLS approach but only the B-cell panel was able to predict a significantly higher risk of relapse and death with increasing resistance index in the clinical data sets. The most sensitive and resistant cell lines, MOLP-2 and RPMI-8226 LR5, respectively, had high leverage, which suggests their differentially expressed genes to possess important predictive value.ConclusionThe present study presents a melphalan resistance index generated by analysis of a B-cell panel of cancer cell lines. However, the resistance index needs to be functionally validated and correlated to known MM biomarkers in independent data sets in order to better understand the mechanism underlying the preparedness to melphalan resistance. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|