Abstract
BackgroundRecent population studies have shown an increase in cancer rates in patients after burn injury over a 30-year follow-up period. This work aims to understand the mediators and mechanisms that lead to cancer susceptibility after acute burn. MethodsIn silico analytics with Watson for Drug Discovery were performed to interrogate networks and pathways in common between burn injury and cancer to better understand the possible mechanistic links. We then useda murine non-severe burn injury model (injury to ∼ 6% body surface area) with subsequent tumor susceptibility evaluation using B16 melanoma challenge 4 weeks after the burn injury. Primary tumor growth (n=10) and metastasis (n=11-13) were assessed compared to sham controls. ResultsNetwork analysis highlighted multiple overlapping pathways important in burn repair and in tumors. In particular, the evidence suggested links to pathways important in the immune response to burn injury (including well characterized pro-inflammatory genes such as IL-6 and TNF-α) and matrix remodeling (such as MMP9) to metastasis. In the murine model, at four weeks after burn injury, primary tumor growth was unaffected (mean volume 353.7mm3± 235.4 vs 256.8mm3± 122.6, burn injury and control respectively, p=0.32). However, mean number of metastases in burn injury mice was significantly increased (7.7± 4.1 compared with 2.6±1.8 for control mice (p=0.0015)), and there was a trend for increased metastatic tumor volume (mean volume 2.7±1.2 compared with 1.6 ±1.3cm3 respectively, p=0.08) after burn injury. ConclusionsThis work suggests burn injury increases cancer susceptibility, specifically through increased number and size of metastases. Further work to delineate the mechanism, potentially through modulation of in silico-identified immune system and metastasis pathways, may provide potential to improve long-term health outcomes for patients. Legal entity responsible for the studyFiona Woods Institute. FundingIBM Watson Health. DisclosureAll authors have declared no conflicts of interest.
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