Prediction of Response to Radiotherapy by Characterizing the Transcriptomic Features in Clinical Tumor Samples across 15 Cancer Types

Abstract

Purpose. Radiotherapy (RT) is one of the major cancer treatments. However, the responses to RT vary among individual patients, partly due to the differences of the status of gene expression and mutation in tumors of patients. Identification of patients who will benefit from RT will improve the efficacy of RT. However, only a few clinical biomarkers were currently used to predict RT response. Our aim is to obtain gene signatures that can be used to predict RT response by analyzing the transcriptome differences between RT responder and nonresponder groups. Materials and Methods. We obtained transcriptome data of 1664 patients treated with RT from the TCGA database across 15 cancer types. First, the genes with a significant difference between RT responder (R group) and nonresponder groups (PD group) were identified, and the top 100 genes were used to build the gene signatures. Then, we developed the predictive model based on binary logistic regression to predict patient response to RT. Results. We identified a series of differentially expressed genes between the two groups, which are involved in cell proliferation, migration, invasion, EMT, and DNA damage repair pathway. Among them, MDC1, UCP2, and RBM45 have been demonstrated to be involved in DNA damage repair and radiosensitivity. Our analysis revealed that the predictive model was highly specific for distinguishing the R and PD patients in different cancer types with an area under the curve (AUC) ranging from 0.772 to 0.972. It also provided a more accurate prediction than that from a single-gene signature for the overall survival (OS) of patients. Conclusion. The predictive model has a potential clinical application as a biomarker to help physicians create optimal treatment plans. Furthermore, some of the genes identified here may be directly involved in radioresistance, providing clues for further studies on the mechanism of radioresistance.