Gene expression profiling has identified cancer prognostic and predictive signatures with superior performance to
conventional histopathological or clinical parameters. Consequently, signatures are being incorporated into clinical practice
and will soon influence everyday decisions in oncology. However, the slight overlap in the gene identity between signatures
for the same cancer type or condition raises questions about their biological and clinical implications. To clarify these issues,
better understanding of the molecular properties and possible interactions underlying apparently dissimilar signatures is
needed. Here, we evaluated whether the signatures of 24 independent studies are related at the genome, transcriptome or
proteome levels. Significant associations were consistently observed across these molecular layers, which suggest the
existence of a common cancer cell phenotype. Convergence on cell proliferation and death supports the pivotal
involvement of these processes in prognosis, metastasis and treatment response. In addition, functional and molecular
associations were identified with the immune response in different cancer types and conditions that complement the
contribution of cell proliferation and death. Examination of additional, independent, cancer datasets corroborated our
observations. This study proposes a comprehensive strategy for interpreting cancer signatures that reveals common design
principles and systems-level properties.
