Radiosensitivity index emerges as a potential biomarker for combined radiotherapy and immunotherapy.
Radiosensitivity index emerges as a potential biomarker for combined radiotherapy and immunotherapy.
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放射敏性指数是用于放射疗法和免疫疗法的潜在生物标志物。
DOI：
10.1038/s41525-021-00200-0
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发表时间：
2021-06-02
影响因子：
5.3
通讯作者：
Huang WY
中科院分区：
文献类型：
--
作者：
Dai YH;Wang YF;Shen PC;Lo CH;Yang JF;Lin CS;Chao HL;Huang WY
在免疫治疗时代，缺乏可靠的基因组预测因子来确定联合放疗和免疫治疗（CRI）的最佳患者群体。本研究的目的是调查是否基因组评分定义放射敏感性与免疫反应。建立了MMD数据集的基因组数据库，建立了肿瘤基因组图谱（TCGA）。根据包含10个基因的秩和回归模型，计算放射敏感性指数（RSI）。共分析了11种主要癌症类型的12832例原发性肿瘤与DNA修复、细胞干性、巨噬细胞极化和免疫亚型的相关性。从MET 500中提取另外585个转移组织。通过临界点0.46将RSI分层为RSI-低和RSI-高。蛋白质组差异分析用于根据RSI类别鉴定重要蛋白质。应用基因集方差分析（GSVA）来测量基因组途径活性（18个基因用于T细胞发炎活性）。生存分析采用Kaplan-Meier法。RSI与同源DNA修复、癌干性和免疫相关分子特征显著相关。较低的RSI与较高的M1巨噬细胞分数相关。差异蛋白质组学分析表明，在RSI低的结直肠肿瘤中，TAP 2表达显著升高。在TCGA队列中，显性干扰素-γ（IFN-γ）应答的特征为RSI较低，并预测对程序性细胞死亡1（PD-1）阻断的应答更好。总之，除了辐射反应外，我们的研究还确定了RSI与各种免疫相关特征相关，并预测了对PD-1阻断的反应，从而突出了其作为CRI候选生物标志物的潜力。
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.
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影响因子：
4.4
作者：
Adhikary T;Wortmann A;Finkernagel F;Lieber S;Nist A;Stiewe T;Wagner U;Müller-Brüsselbach S;Reinartz S;Müller R
通讯作者：
Müller R
影响因子：
11.5
作者：
Eschrich, Steven A.;Fulp, William J.;Torres-Roca, Javier F.
通讯作者：
Torres-Roca, Javier F.
影响因子：
8.8
作者：
Abiko, K.;Matsumura, N.;Hamanishi, J.;Horikawa, N.;Murakami, R.;Yamaguchi, K.;Yoshioka, Y.;Baba, T.;Konishi, I.;Mandai, M.
通讯作者：
Mandai, M.
DOI：
10.1158/1078-0432.ccr-18-0825
发表时间：
2018-10-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Cui Y;Li B;Pollom EL;Horst KC;Li R
通讯作者：
Li R
DOI：
10.1158/1078-0432.ccr-18-0784
发表时间：
2018-10-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Chen GM;Kannan L;Geistlinger L;Kofia V;Safikhani Z;Gendoo DMA;Parmigiani G;Birrer M;Haibe-Kains B;Waldron L
通讯作者：
Waldron L