Abstract
Background Chronic Lymphocytic Leukemia (CLL) presents two subtypes which have drastically different clinical outcomes. So far, these two subtypes are not associated to clear differences in gene expression profiles. Interestingly, recent results have highlighted important roles for heterogeneity, both at the genetic and at the epigenetic level in CLL progression.
Results We propose to use gene expression variability across patients to investigate differences between the two CLL subtypes. We find that the most aggressive type of this disease shows higher variability of gene expression across patients and we elaborate on this observation to produce a method that classifies patients into clinical subtypes. Finally, we find that, overall, genes that show higher variability in the aggressive subtype are related to cell cycle, development and inter-cellular communication, probably related to faster progression of this disease subtype.
Conclusions There are strong relations between disease subtype and gene expression variability linking significantly increased expression variability to phenotypes such as aggressiveness and resistance to therapy in CLL.
List of abbreviations
- AUC
- Area Under the Curve
- CLL
- Chronic Lymphocytic Leukemia
- CV
- Coefficient of Variation
- DV
- Differential Variability
- EV
- Expression Variability measure of Alemu et al.
- FDR
- False Discovery Rate
- ICGC
- International Cancer Genome Consortium
- ROC
- Receiver Operating Characteristic