Abstract 4262: Inflammatory gene expression differences among prostate cancer patients exposed to the World Trade Center aftermath
Authors: Hashim Dana , Gong Yixuan , Galsky Matthew , Baker Charles , Boffetta Paolo , Donovan Michael J. , Taioli Emanuela , Oh William K. 
Published: July 2017

Background: World Trade Center (WTC) rescue and recovery workers were exposed to a complex mixture of dust and debris after the collapse of the WTC towers. An excess incidence of prostate cancer was observed in the WTC workers and, more advanced prostate cancer cases have been associated with higher levels of WTC exposure. As inflammation is known to promote tumor development and progression and the prostate cancer etiology remains uncertain, we compared RNA expression of inflammatory markers in prostate cancer tumors from WTC patients with matched prostate cancer patients not related to WTC.

Methods: RNA was prepared from formalin-fixed paraffin embedded tumors of 15 WTC prostate cancer and 14 non-WTC prostate cancers, age, race, and Gleason-score matched. Gene expression was quantified using Nanostring nCounter® PanCancer Immune Profiling Panel, which combines markers for 24 immune cell types and populations, 30 common cancer antigens and genes representing all immune response categories including key checkpoint blockade genes. Data analysis was performed using the NanoString nSolver 2.6 analysis software. Genes shown to be characteristic of innate and adaptive immune cell populations were used to derive cell-type scores indicating population abundance of each immune cell type. Comparisons of cell type scores were performed using Student’s t test.

Results: WTC prostate cancers expressed high levels of genes associated with chronic inflammation: NFATC2 (Fold change=3.0, P&lt;0.001), MRC1 (Fold change=2.0, P=0.001), CT8L (Fold change=1.5, P=0.01), CSF1 (Fold change=1.5, P=0.001), NFKB1 (Fold change=1.3, P=0.005), CXCL13 (Fold change=3.7, P=0.04), IL6 (Fold change=2.5, P=0.04) and ITCH (Fold change= 0.3, P=0.001) compared with non-WTC prostate cancers. Conversely, non-WTC prostate cancers expressed higher levels of genes associated with innate immunity: TIRAP (Fold Change=0.05, P&lt;0.001), IRF3 (Fold change=1, P&lt;0.001), and FADD (Fold change=0.5, P=0.005), compared with WTC prostate cancer. In cell type enrichment analysis, macrophage and CD45+ cells scored higher in non-WTC (8.83±0.75 SD and 9.09±0.78 SD) than WTC (7.81±0.73 SD and 8.53±0.53 SD) prostate cancer samples (t=3.70, P&lt;0.001 and t=2.29, P=0.02); regulatory T cells scored higher in WTC (5.90±0.52 SD) than non-WTC (5.42±0.67 SD) prostate cancer samples (t=2.15, P=0.04).

Conclusions: Compared to non-WTC prostate cancers, tumors from WTC-exposed patients show overall lower expressions of genes involved in local innate immune-system response and a higher expression of adaptive immune-system response genes. Environmental factors, such as exposure during the 9/11 aftermath, may have played a role in the development of advanced prostate cancer in these patients via high immune-tolerance. The results have implications for a role of environmental factors in prostate carcinogenesis.

Citation Format: Dana Hashim, Yixuan Gong, Matthew Galsky, Charles Baker, Paolo Boffetta, Michael J. Donovan, Emanuela Taioli, William K. Oh. Inflammatory gene expression differences among prostate cancer patients exposed to the World Trade Center aftermath [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4262. doi:10.1158/1538-7445.AM2017-4262