抗辐射性
辐射敏感性
癌症研究
医学
头颈部鳞状细胞癌
生物
癌症
肿瘤科
放射治疗
头颈部癌
细胞周期
细胞
内科学
细胞培养
遗传学
作者
Guangqi Li,Yufei Jiang,Guang Li,Qiao Qiao
标识
DOI:10.1016/j.radonc.2021.03.017
摘要
Abstract
Background
Radioresistance is a major barrier to the successful treatment of head and neck squamous cell carcinoma (HNSCC). Methods
We took advantage of different types of data, including single-cell sequencing data, bulk tissue sequencing data and deconvolution data, to conduct a comprehensive analysis of HNSCC radiosensitivity at the cellular, patient, and cell type levels. Single-cell transcriptomes for 1388 primary cancer cells from a previous study were analysed. The TCGA HNSCC dataset including 499 primary HNSCC samples with RNA-seq data, DNA methylation data and clinical information were used for bulk tissue sequencing analyses and deconvolution. Results
We found that radiosensitivity clustering of HNSCC cells was highly consistent with molecular typing, where cancer cells of the atypical subtype exhibited a higher sensitivity than those of the classical and basal subtypes. The common radioresistant gene modules of the classical and basal subtypes were mainly associated with cell division and cell cycle regulation; the classical subtype specific radioresistant module was mainly associated with metabolic pathways; and the basal radioresistant subtype specific modules included two epithelial differentiation-related modules and a module mainly associated with endoplasmic reticulum, apoptosis and focal adhesion. We developed a radioresistance score using genes that affect both the cancer cell response to radiation and the patient response to radiotherapy. An enhanced cancer-immune interaction through the PD1-PDL1/PDL2 and TIM3-Galectin9 pathways was observed in radioresistant tumours, with foldchange = 2.88 (PD1), 1.44 (PDL1), 3.22 (PDL2), 1.47 (TIM3), 1.88 (Galectin9) respectively and FDR < 0.001. Transcriptional activities related to the hypoxia response, p53 pathway, NF-kappa-B pathway and inflammatory response were abnormally activated in the radioresistant tumours (FDR < 0.05). Conclusions
This study comprehensively discussed the radioresistance of HNSCC, identified a group of HNSCCs that were likely to benefit from combined radiotherapy and immune checkpoint blockade, and proposed new targets for the treatment of radioresistant HNSCC.
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