Radiosensitivity index emerges as a potential biomarker for combined radiotherapy and immunotherapy

Yang Hong Dai, Ying Fu Wang, Po Chien Shen, Cheng Hsiang Lo, Jen Fu Yang, Chun Shu Lin, Hsing Lung Chao, Wen Yen Huang

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

In the era of immunotherapy, there lacks of a reliable genomic predictor to identify optimal patient populations in combined radiotherapy and immunotherapy (CRI). The purpose of this study is to investigate whether genomic scores defining radiosensitivity are associated with immune response. Genomic data from Merged Microarray-Acquired dataset (MMD) were established and the Cancer Genome Atlas (TCGA) were obtained. Based on rank-based regression model including 10 genes, radiosensitivity index (RSI) was calculated. A total of 12832 primary tumours across 11 major cancer types were analysed for the association with DNA repair, cellular stemness, macrophage polarisation, and immune subtypes. Additional 585 metastatic tissues were extracted from MET500. RSI was stratified into RSI-Low and RSI-High by a cutpoint of 0.46. Proteomic differential analysis was used to identify significant proteins according to RSI categories. Gene Set Variance Analysis (GSVA) was applied to measure the genomic pathway activity (18 genes for T-cell inflamed activity). Kaplan-Meier analysis was performed for survival analysis. RSI was significantly associated with homologous DNA repair, cancer stemness and immune-related molecular features. Lower RSI was associated with higher fraction of M1 macrophage. Differential proteomic analysis identified significantly higher TAP2 expression in RSI-Low colorectal tumours. In the TCGA cohort, dominant interferon-γ (IFN-γ) response was characterised by low RSI and predicted better response to programmed cell death 1 (PD-1) blockade. In conclusion, in addition to radiation response, our study identified RSI to be associated with various immune-related features and predicted response to PD-1 blockade, thus, highlighting its potential as a candidate biomarker for CRI.

Original languageEnglish
Article number40
Journalnpj Genomic Medicine
Volume6
Issue number1
DOIs
Publication statusPublished - Dec 2021

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

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