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Abstract
High-charge, high-energy ion particle (HZE) radiations are extraterrestrial in origin and characterized by high linear energy transfer (high-LET), which causes more severe cell damage than low-LET radiations like γ-rays or photons. High-LET radiation poses potential cancer risks for astronauts on deep space missions, but the studies of its carcinogenic effects have relied heavily on animal models. It remains uncertain whether such data are applicable to human disease. Here, we used genomics approaches to directly compare high-LET radiation-induced, low-LET radiation-induced and spontaneous hepatocellular carcinoma (HCC) in mice with a human HCC cohort from The Cancer Genome Atlas (TCGA). We identified common molecular pathways between mouse and human HCC and discovered a subset of orthologous genes (mR-HCC) that associated high-LET radiation-induced mouse HCC with a subgroup (mrHCC2) of the TCGA cohort. The mrHCC2 TCGA cohort was more enriched with tumor-suppressing immune cells and showed a better prognostic outcome than other patient subgroups.
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Details
1 The University of Texas Southwestern Medical Center, Department of Radiation Oncology, Dallas, USA (GRID:grid.267313.2) (ISNI:0000 0000 9482 7121)
2 The University of Texas Medical Branch, Department of Radiation Oncology, Galveston, USA (GRID:grid.176731.5) (ISNI:0000 0001 1547 9964)
3 Frederick National Laboratory for Cancer Research, Frederick, USA (GRID:grid.418021.e) (ISNI:0000 0004 0535 8394)
4 Colorado State University, Department of Environmental and Radiological Health Sciences, Fort Collins, USA (GRID:grid.47894.36) (ISNI:0000 0004 1936 8083)
5 NASA Johnson Space Center, Houston, USA (GRID:grid.419085.1) (ISNI:0000 0004 0613 2864)
6 Radiation Effects Research Foundation, Hiroshima, Japan (GRID:grid.418889.4) (ISNI:0000 0001 2198 115X)
7 The University of Texas Southwestern Medical Center, Department of Radiation Oncology, Dallas, USA (GRID:grid.267313.2) (ISNI:0000 0000 9482 7121); The University of Texas Southwestern Medical Center, Harold C. Simmons Comprehensive Cancer Center, Dallas, USA (GRID:grid.267313.2) (ISNI:0000 0000 9482 7121)