Gene expression risk signatures maintain prognostic power in multiple myeloma despite microarray probe set translation

TY - JOUR

T1 - Gene expression risk signatures maintain prognostic power in multiple myeloma despite microarray probe set translation

AU - Hermansen, N E U

AU - Borup, R

AU - Andersen, M K

AU - Vangsted, A J

AU - Clausen, T N

AU - Kristensen, D L

AU - Nielsen, F C

AU - Gimsing, P

N1 - © 2016 John Wiley & Sons Ltd.

PY - 2016/6/1

Y1 - 2016/6/1

N2 - INTRODUCTION: Gene expression profiling (GEP) risk models in multiple myeloma are based on 3'-end microarrays. We hypothesized that GEP risk signatures could retain prognostic power despite being translated and applied to whole-transcript microarray data.METHODS: We studied CD138-positive bone marrow plasma cells in a prospective cohort of 59 samples from newly diagnosed patients eligible for high-dose therapy (HDT) and 67 samples from previous HDT patients with progressive disease. We used Affymetrix Human Gene 1.1 ST microarrays for GEP. Nine GEP risk signatures were translated by probe set match and applied to our data in multivariate Cox regression analysis for progression-free survival and overall survival in combination with clinical, cytogenetic and biochemical risk markers, including the International Staging System (ISS).RESULTS: Median follow-up was 66 months (range 42-87). Various translated GEP risk signatures or combinations hereof were significantly correlated with survival: among newly diagnosed patients mainly in combination with cytogenetic high-risk markers and among relapsed patients mainly in combination with ISS stage III.CONCLUSION: Translated GEP risk signatures maintain significant prognostic power in HDT myeloma patients. We suggest probe set matching for GEP risk signature translation as part of the efforts towards a microarray-independent GEP risk standard. (ClicinalTrials.gov identifier: NCT00639054).

AB - INTRODUCTION: Gene expression profiling (GEP) risk models in multiple myeloma are based on 3'-end microarrays. We hypothesized that GEP risk signatures could retain prognostic power despite being translated and applied to whole-transcript microarray data.METHODS: We studied CD138-positive bone marrow plasma cells in a prospective cohort of 59 samples from newly diagnosed patients eligible for high-dose therapy (HDT) and 67 samples from previous HDT patients with progressive disease. We used Affymetrix Human Gene 1.1 ST microarrays for GEP. Nine GEP risk signatures were translated by probe set match and applied to our data in multivariate Cox regression analysis for progression-free survival and overall survival in combination with clinical, cytogenetic and biochemical risk markers, including the International Staging System (ISS).RESULTS: Median follow-up was 66 months (range 42-87). Various translated GEP risk signatures or combinations hereof were significantly correlated with survival: among newly diagnosed patients mainly in combination with cytogenetic high-risk markers and among relapsed patients mainly in combination with ISS stage III.CONCLUSION: Translated GEP risk signatures maintain significant prognostic power in HDT myeloma patients. We suggest probe set matching for GEP risk signature translation as part of the efforts towards a microarray-independent GEP risk standard. (ClicinalTrials.gov identifier: NCT00639054).

KW - Adult

KW - Aged

KW - Disease-Free Survival

KW - Female

KW - Follow-Up Studies

KW - Gene Expression Profiling

KW - Gene Expression Regulation, Neoplastic

KW - Humans

KW - Male

KW - Middle Aged

KW - Multiple Myeloma

KW - Oligonucleotide Array Sequence Analysis

KW - Survival Rate

KW - Clinical Trial

KW - Journal Article

KW - Multicenter Study

U2 - 10.1111/ijlh.12486

DO - 10.1111/ijlh.12486

M3 - Journal article

C2 - 27027250

SN - 1751-5521

VL - 38

SP - 298

EP - 307

JO - Clinical and Laboratory Haematology

JF - Clinical and Laboratory Haematology

IS - 3

ER -