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

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...

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Autores principales:	Yang-Hong Dai, Ying-Fu Wang, Po-Chien Shen, Cheng-Hsiang Lo, Jen-Fu Yang, Chun-Shu Lin, Hsing-Lung Chao, Wen-Yen Huang
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Genetics QH426-470
Acceso en línea:	https://doaj.org/article/4214af13ccb94d3a95aa527a65bc27ae
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spelling	oai:doaj.org-article:4214af13ccb94d3a95aa527a65bc27ae2021-12-02T17:51:22ZRadiosensitivity index emerges as a potential biomarker for combined radiotherapy and immunotherapy10.1038/s41525-021-00200-02056-7944https://doaj.org/article/4214af13ccb94d3a95aa527a65bc27ae2021-06-01T00:00:00Zhttps://doi.org/10.1038/s41525-021-00200-0https://doaj.org/toc/2056-7944Abstract 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.Yang-Hong DaiYing-Fu WangPo-Chien ShenCheng-Hsiang LoJen-Fu YangChun-Shu LinHsing-Lung ChaoWen-Yen HuangNature PortfolioarticleMedicineRGeneticsQH426-470ENnpj Genomic Medicine, Vol 6, Iss 1, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Genetics QH426-470
spellingShingle	Medicine R Genetics QH426-470 Yang-Hong Dai Ying-Fu Wang Po-Chien Shen Cheng-Hsiang Lo Jen-Fu Yang Chun-Shu Lin Hsing-Lung Chao Wen-Yen Huang Radiosensitivity index emerges as a potential biomarker for combined radiotherapy and immunotherapy
description	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.
format	article
author	Yang-Hong Dai Ying-Fu Wang Po-Chien Shen Cheng-Hsiang Lo Jen-Fu Yang Chun-Shu Lin Hsing-Lung Chao Wen-Yen Huang
author_facet	Yang-Hong Dai Ying-Fu Wang Po-Chien Shen Cheng-Hsiang Lo Jen-Fu Yang Chun-Shu Lin Hsing-Lung Chao Wen-Yen Huang
author_sort	Yang-Hong Dai
title	Radiosensitivity index emerges as a potential biomarker for combined radiotherapy and immunotherapy
title_short	Radiosensitivity index emerges as a potential biomarker for combined radiotherapy and immunotherapy
title_full	Radiosensitivity index emerges as a potential biomarker for combined radiotherapy and immunotherapy
title_fullStr	Radiosensitivity index emerges as a potential biomarker for combined radiotherapy and immunotherapy
title_full_unstemmed	Radiosensitivity index emerges as a potential biomarker for combined radiotherapy and immunotherapy
title_sort	radiosensitivity index emerges as a potential biomarker for combined radiotherapy and immunotherapy
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/4214af13ccb94d3a95aa527a65bc27ae
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Radiosensitivity index emerges as a potential biomarker for combined radiotherapy and immunotherapy

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