Lyu Haoyu, Li Mengyuan, Jiang Zehang, Liu Zhixian, Wang Xiaosheng
Biomedical Informatics Research Lab, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing 211198, China.
Cancer Genomics Research Center, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing 211198, China.
Comput Struct Biotechnol J. 2019 Jul 26;17:1020-1030. doi: 10.1016/j.csbj.2019.07.009. eCollection 2019.
Although immunotherapy has emerged as an effective therapeutic strategy for various cancers including head and neck squamous cell carcinomas (HNSCCs), only a subset of patients can benefit from such therapy. Hence, it is pressing to discover predictive biomarkers for cancer immunotherapy response. and mutations frequently occur in HNSCC and correlate with a worse prognosis in HNSCC. We extensively characterized the associations of mutations and mutations with HNSCC immunity based on multiple cancer genomics datasets. We compared the enrichment levels of 20 immune signatures between -mutated and -wildtype HNSCCs, and between -mutated and -wildtype HNSCCs, and found that mutations were associated with depressed immune signatures while mutations were associated with enhanced immune signatures in HNSCC. Moreover, we found multiple p53- and RAS-mediated pathways showing significant correlations with HNSCC immunity. Furthermore, we demonstrated that the association between mutation and tumor immunity was independent of the human papillomavirus (HPV) infection and smoking status in HNSCC. These data suggest that p53 and RAS may play important roles in regulating HNSCC immunity and that the and mutation status could be useful biomarkers for stratifying HNSCC patients responsive to immunotherapy.
尽管免疫疗法已成为包括头颈部鳞状细胞癌（HNSCC）在内的各种癌症的有效治疗策略，但只有一部分患者能从这种疗法中受益。因此，迫切需要发现癌症免疫治疗反应的预测生物标志物。p53和RAS突变在HNSCC中频繁发生，且与HNSCC的较差预后相关。我们基于多个癌症基因组数据集广泛表征了p53突变和RAS突变与HNSCC免疫的关联。我们比较了p53突变型和p53野生型HNSCC之间以及RAS突变型和RAS野生型HNSCC之间20种免疫特征的富集水平，发现p53突变与HNSCC中免疫特征的降低相关，而RAS突变与HNSCC中免疫特征的增强相关。此外，我们发现多个p53和RAS介导的途径与HNSCC免疫显示出显著相关性。此外，我们证明了p53突变与肿瘤免疫之间的关联独立于HNSCC中的人乳头瘤病毒（HPV）感染和吸烟状态。这些数据表明，p53和RAS可能在调节HNSCC免疫中起重要作用，并且p53和RAS突变状态可能是对免疫治疗有反应的HNSCC患者分层的有用生物标志物。
