Qiang Weijie, Dai Yifei, Xing Xiaoyan, Sun Xiaobo
Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100193, PR China.
Key Laboratory of New Drug Discovery based on Classic Chinese Medicine Prescription, Chinese Academy of Medical Sciences, Beijing 100193, PR China.
Comput Struct Biotechnol J. 2021 Feb 9;19:1263-1276. doi: 10.1016/j.csbj.2021.01.046. eCollection 2021.
Immunotherapy has become a promising therapeutic option for Head and neck squamous cell carcinoma (HNSC). However, only a small percentage of patients could benefit from it, and the overall prognosis was far from satisfactory. In this study, by comprehensively computational analyses of hundreds of HNSC samples, a prognostic signature composed of 13 immune-related genes (IRGs) was constructed. The results of the analyses in multiple datasets indicated that our signature had high predictive accuracy and could serve as an independent prognostic predictor. Based on this signature and multiple clinical variables, we also established a prognostic nomogram to quantitatively predict the survival risk of individual patients. Moreover, this signature could accurately predict survival, reflect the immune microenvironment, and predict immunotherapy efficacy among HNSC patients. Two potential drugs (doxorubicin and daunorubicin) were also identified via Connectivity Map and molecular docking, which could be used for HNSC combination therapy. Taken together, we developed and validated a robust IRG-based prognostic signature to monitor the prognosis of HNSC, which could provide a solid foundation for individualized cancer immunotherapy.
免疫疗法已成为头颈部鳞状细胞癌(HNSC)一种很有前景的治疗选择。然而,只有一小部分患者能从中受益,总体预后远不尽人意。在本研究中,通过对数百份HNSC样本进行全面的计算分析,构建了一个由13个免疫相关基因(IRG)组成的预后特征。多个数据集中的分析结果表明,我们构建的特征具有较高的预测准确性,可作为独立的预后预测指标。基于此特征和多个临床变量,我们还建立了一个预后列线图,以定量预测个体患者的生存风险。此外,该特征能够准确预测HNSC患者的生存情况,反映免疫微环境,并预测免疫治疗疗效。通过连通图和分子对接还鉴定出两种潜在药物(阿霉素和柔红霉素),可用于HNSC联合治疗。综上所述,我们开发并验证了一种基于IRG的强大预后特征以监测HNSC的预后,这可为个体化癌症免疫治疗提供坚实基础。