Integration of immune and hypoxia gene signatures improves the prediction of radiosensitivity in breast cancer.

Immunity and hypoxia are two important factors that affect the response of cancer patients to radiotherapy. At the same time, considering the limited predictive value of a single predictive model and the uncertainty of grouping patients near the cutoff value, we developed and validated a combined model based on immune- and hypoxia-related gene expression profiles to predict the radiosensitivity of breast cancer patients. This study was based on breast cancer data from The Cancer Genome Atlas (TCGA). Spike-and-slab Lasso regression analysis was performed to select three immune-related genes and develop a radiosensitivity model. Lasso Cox regression modeling selected 11 hypoxia-related genes for development of radiosensitivity model. Three independent datasets (Molecular Taxonomy of Breast Cancer International Consortium [METABRIC], E-TABM-158, GSE103746) were used to validate the predictive value of radiosensitivity signatures. In the TCGA dataset, the 10-year survival probabilities of the immune radioresistant (IRR) and hypoxia radioresistant (HRR) groups were 0.189 (0.037, 0.973) and 0.477 (0.293, 0.776), respectively. The 10-year survival probabilities of the immune radiosensitive (IRS) and hypoxia radiosensitive (HRS) groups were 0.778 (0.676, 0.895) and 0.824 (0.723, 0.939), respectively. Based on these two gene signatures, we further constructed a combined model and divided all patients into three groups (IRS/HRS, mixed, IRR/HRR). We identified the IRS/HRS patients most likely to benefit from radiotherapy; the 10-year survival probability was 0.886 (0.806, 0.976). The 10-year survival probability of the IRR/HRR group was 0. In conclusion, a combined model integrating immune- and hypoxia-related gene signatures could effectively predict the radiosensitivity of breast cancer and more accurately identify radiosensitive and radioresistant patients than a single model. AJCR