Cao Minghui, Xiao Liwei, Chen Shuo, Huang Jiaming
Department of Radiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, China.
Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Medical Research Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, China.
Discov Oncol. 2024 Jan 31;15(1):23. doi: 10.1007/s12672-024-00859-8.
The hypoxia-responsive state of cancer is a complex pathophysiological process involving numerous genes playing different roles. Due to the rapid proliferation of cancer cells and chaotic angiogenesis, the clinical features of hypoxia-responsive states are not yet clear in patients with ovarian cancer.
Based on the RNA expression levels of 14 hypoxic markers, our study screened out hypoxia-related genes and construct a hypoxic score pattern to quantify the hypoxia-responsive states of a single tumor. Combining clinical prognosis, tumor mutation burden, microsatellite instability, the expression level of the immune checkpoint, IC50, and other indicators to evaluate the impact of different hypoxia-responsive states on clinical prognosis and therapeutic sensitivity.
Our study identified a subgroup with an active hypoxia-responsive state and they have a worse clinical prognosis but exhibit higher immunogenicity and higher sensitivity to immunotherapy.
This work revealed that hypoxia-responsive states played an important role in formation of tumor immunogenicity. Evaluating the hypoxia-responsive state will contribute to guiding more effective immunotherapy strategies.
癌症的缺氧反应状态是一个复杂的病理生理过程,涉及众多发挥不同作用的基因。由于癌细胞的快速增殖和混乱的血管生成,卵巢癌患者缺氧反应状态的临床特征尚不清楚。
基于14种缺氧标志物的RNA表达水平,我们的研究筛选出缺氧相关基因,并构建缺氧评分模式以量化单个肿瘤的缺氧反应状态。结合临床预后、肿瘤突变负荷、微卫星不稳定性、免疫检查点的表达水平、半数抑制浓度(IC50)等指标,评估不同缺氧反应状态对临床预后和治疗敏感性的影响。
我们的研究鉴定出一个具有活跃缺氧反应状态的亚组,他们的临床预后较差,但具有更高的免疫原性和对免疫治疗更高的敏感性。
这项工作揭示了缺氧反应状态在肿瘤免疫原性形成中起重要作用。评估缺氧反应状态将有助于指导更有效的免疫治疗策略。