ArticleCancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology2023
Deep Transcriptome Profiling of Multiple Myeloma Using Quantitative Phenotypes.
Article in Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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6 authors at 1 institution in 1 country.
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Abstract
backgroundTranscriptome studies are gaining momentum in genomic epidemiology, and the need to incorporate these data in multivariable models alongside other risk factors brings demands for new approaches.
methodsHere we describe SPECTRA, an approach to derive quantitative variables that capture the intrinsic variation in gene expression of a tissue type. We applied the SPECTRA approach to bulk RNA sequencing from malignant cells (CD138+) in patients from the Multiple Myeloma Research Foundation CoMMpass study.
resultsA set of 39 spectra variables were derived to represent multiple myeloma cells. We used these variables in predictive modeling to determine spectra-based risk scores for overall survival, progression-free survival, and time to treatment failure. Risk scores added predictive value beyond known clinical and expression risk factors and replicated in an external dataset. Spectrum variable S5, a significant predictor for all three outcomes, showed pre-ranked gene set enrichment for the unfolded protein response, a mechanism targeted by proteasome inhibitors which are a common first line agent in multiple myeloma treatment. We further used the 39 spectra variables in descriptive modeling, with significant associations found with tumor cytogenetics, race, gender, and age at diagnosis; factors known to influence multiple myeloma incidence or progression.
conclusionsQuantitative variables from the SPECTRA approach can predict clinical outcomes in multiple myeloma and provide a new avenue for insight into tumor differences by demographic groups. IMPACT: The SPECTRA approach provides a set of quantitative phenotypes that deeply profile a tissue and allows for more comprehensive modeling of gene expression with other risk factors.
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