Journal
ONCOTARGET
Volume 8, Issue 24, Pages 38668-38681Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.16961
Keywords
cell proliferation; cancer; reelin; survival; RNA-seq
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Funding
- State Cancer Fund of Alabama
- UAB MSTP [NIH-NIGMS 5T32GM008361-21]
- William J. Maier III Fellowship in Cancer Prevention (Prevent Cancer Foundation)
- HudsonAlpha Tie the Ribbons Fund
- UAB CCTS grant [NIH 1UL1TR001417-01]
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Despite advances in cancer diagnosis and treatment strategies, robust prognostic signatures remain elusive in most cancers. Cell proliferation has long been recognized as a prognostic marker in cancer, but the generation of comprehensive, publicly available datasets allows examination of the links between cell proliferation and cancer characteristics such as mutation rate, stage, and patient outcomes. Here we explore the role of cell proliferation across 19 cancers (n = 6,581 patients) by using tissuebased RNA sequencing data from The Cancer Genome Atlas Project and calculating a 'proliferative index' derived from gene expression associated with Proliferating Cell Nuclear Antigen (PCNA) levels. This proliferative index is significantly associated with patient survival (Cox, p-value < 0.05) in 7 of 19 cancers, which we have defined as proliferation-informative cancers (PICs). In PICs, the proliferative index is strongly correlated with tumor stage and nodal invasion. PICs demonstrate reduced baseline expression of proliferation machinery relative to non-PICs. Additionally, we find the proliferative index is significantly associated with gross somatic mutation burden (Spearman, p= 1.76 x 10-23) as well as with mutations in individual driver genes. This analysis provides a comprehensive characterization of tumor proliferation indices and their association with disease progression and prognosis in multiple cancer types and highlights specific cancers that may be particularly susceptible to improved targeting of this classic cancer hallmark.
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