Abstract 491P
Background
Progression and recurrence of disease due to treatment failure remains a major challenge of cancer clinical management. We investigated the role of interleukin-1 receptor-associated kinase 1 (IRAK1) in cancer progression, recurrence and therapeutic resistance.
Methods
Immunogenomic analysis from TCGA data was performed. Statistical analyses were performed for expression and distribution of IRAK1, tumor infiltrating immune cells fraction and oncogenic signaling pathways in each tumor. Cox proportional hazards model was used to evaluate the association of IRAK1 with clinical survival outcomes.
Results
IRAK1 mRNA expression and distribution in 11,160 patients across 33 cancers from the TCGA data was analyzed. IRAK1 expression was associated with a poor progression free survival (PFS) in univariate (HR=1.65, p<0.01) and multivariate (HR=1.47, p<0.01) analysis after adjusting for age, gender, race, stage and cancer grade. IRAK1 expression was associated with IFN-g dominant immune subtype (p<0.01), and M1/M2 macrophage polarization (0.05/0.25; p<0.01) with high proliferation rate (corr= 0.38, p<0.01). IRAK1 expression was positively correlated with Homologous Recombination Defects (corr= 0.34, p<0.01), SNV Neoantigens count (65.03/105.25 [(low/high)], p<0.01), Indel Neoantigens (83.51/101.23, p<0.01), BCR Richness (44.08/70.36, p<0.01). A positive relationship with Dendritic Cells Activated (p<0.01) and Th2 Cells (p<0.01), while negative correlated with T cell CD8+ (p<0.01), Th1 (p<0.01) and Th17 Cells (p<0.01). Positive relation was observed with oncogenic signaling pathways of Cell Cycle (OR 2.62; p < 0.01), Hippo (OR 1.35; p < 0.01), MYC (OR 1.97; p < 0.01), NOTCH (OR 1.77; p < 0.01), NRF2 (OR 3.19; p < 0.01), PI3K (OR 1.39; p < 0.01), RTK RAS (OR 1.21; p < 0.01), TP53 (OR 3.65; p < 0.01), TGF-Beta (OR 1.70; p < 0.01), WNT (OR 1.47; p < 0.01). IRAK1 was also associated with poor clinical outcomes in multiple cancer types.
Conclusions
IRAK1 expression is associated with poor clinical outcomes, where it acts to drive aggressive growth, metastasis and resistance to treatment. IRAK1 might be valuable target indicating opportunities for personalized cancer therapy.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
N. Kumar.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.