Xiao Kai, Tan Jun, Yuan Jian, Peng Gang, Long Wenyong, Su Jun, Xiao Yao, Xiao Qun, Wu Changwu, Qin Chaoying, Hu Lili, Liu Kaili, Liu Shunlian, Zhou Hao, Ning Yichong, Ding Xiaofeng, Liu Qing
Department of Neurosurgery, Xiangya Hospital of Central South University, Changsha, China.
Institute of Skull Base Surgery and Neuro-oncology at Hunan, Changsha, China.
J Cell Mol Med. 2020 Nov;24(22):13235-13247. doi: 10.1111/jcmm.15939. Epub 2020 Oct 3.
Glioblastoma (GBM) is a malignant intracranial tumour with the highest proportion and lethality. It is characterized by invasiveness and heterogeneity. However, the currently available therapies are not curative. As an essential environmental cue that maintains glioma stem cells, hypoxia is considered the cause of tumour resistance to chemotherapy and radiation. Growing evidence shows that immunotherapy focusing on the tumour microenvironment is an effective treatment for GBM; however, the current clinicopathological features cannot predict the response to immunotherapy and provide accurate guidance for immunotherapy. Based on the ESTIMATE algorithm, GBM cases of The Cancer Genome Atlas (TCGA) data set were classified into high- and low-immune/stromal score groups, and a four-gene tumour environment-related model was constructed. This model exhibited good efficiency at forecasting short- and long-term prognosis and could also act as an independent prognostic biomarker. Additionally, this model and four of its genes (CLECL5A, SERPING1, CHI3L1 and C1R) were found to be associated with immune cell infiltration, and further study demonstrated that these four genes might drive the hypoxic phenotype of perinecrotic GBM, which affects hypoxia-induced glioma stemness. Therefore, these might be important candidates for immunotherapy of GBM and deserve further exploration.
胶质母细胞瘤（GBM）是一种恶性颅内肿瘤，其比例和致死率最高。它具有侵袭性和异质性的特征。然而，目前可用的治疗方法并不能治愈。作为维持胶质瘤干细胞的重要环境线索，缺氧被认为是肿瘤对化疗和放疗产生抗性的原因。越来越多的证据表明，针对肿瘤微环境的免疫疗法是治疗GBM的有效方法；然而，目前的临床病理特征无法预测免疫治疗的反应，也无法为免疫治疗提供准确的指导。基于ESTIMATE算法，将癌症基因组图谱（TCGA）数据集中的GBM病例分为高免疫/基质评分组和低免疫/基质评分组，并构建了一个四基因肿瘤环境相关模型。该模型在预测短期和长期预后方面表现出良好的效率，还可作为独立的预后生物标志物。此外，发现该模型及其四个基因（CLECL5A、SERPING1、CHI3L1和C1R）与免疫细胞浸润有关，进一步研究表明这四个基因可能驱动坏死周围GBM的缺氧表型，从而影响缺氧诱导的胶质瘤干性。因此，这些可能是GBM免疫治疗的重要候选物，值得进一步探索。
