State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Department of Head and Neck Oncology, West China Hospital of Stomatology, Sichuan University, NO.14, 3rd Section of Ren Min Nan Rd., Chengdu, 610041, Sichuan, China.
State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Department of General and Emergency Dentistry, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
BMC Cancer. 2021 Sep 16;21(1):1035. doi: 10.1186/s12885-021-08765-w.
Tumor protein p53 (TP53) is the most frequently mutated gene in head and neck squamous cell carcinoma (HNSC), and TP53 mutations are associated with inhibited immune signatures and poor prognosis. We established a TP53 mutation associated risk score model to evaluate the prognosis and therapeutic responses of patients with HNSC.
Differentially expressed genes between patients with and without TP53 mutations were determined by using data from the HNSC cohort in The Cancer Genome Atlas database. Patients with HNSC were divided into high- and low-risk groups based on a prognostic risk score that was generated from ten TP53 mutation associated genes via the multivariate Cox regression model.
TP53 was the most common mutant gene in HNSC, and TP53 mutations were associated with immunogenic signatures, including the infiltration of immune cells and expression of immune-associated genes. Patients in the high-risk group had significantly poorer overall survival than those in the low-risk group. The high-risk group showed less response to anti-programmed cell death protein 1 (PD-1) therapy but high sensitivity to some chemotherapies.
The risk score based on our TP53 mutation model was associated with poorer survival and could act as a specific predictor for assessing prognosis and therapeutic response in patients with HNSC.
肿瘤蛋白 p53(TP53)是头颈部鳞状细胞癌(HNSC)中最常发生突变的基因,TP53 突变与抑制的免疫特征和不良预后相关。我们建立了一个与 TP53 突变相关的风险评分模型,以评估 HNSC 患者的预后和治疗反应。
通过使用来自癌症基因组图谱数据库中 HNSC 队列的数据,确定了伴有和不伴有 TP53 突变的患者之间的差异表达基因。通过多变量 Cox 回归模型,基于十个与 TP53 突变相关的基因生成的预后风险评分,将 HNSC 患者分为高风险组和低风险组。
TP53 是 HNSC 中最常见的突变基因,TP53 突变与免疫原性特征相关,包括免疫细胞浸润和免疫相关基因的表达。高风险组患者的总生存率明显低于低风险组患者。高风险组对抗程序性细胞死亡蛋白 1(PD-1)治疗的反应较差,但对某些化疗药物的敏感性较高。
基于我们的 TP53 突变模型的风险评分与较差的生存相关,可作为评估 HNSC 患者预后和治疗反应的特定预测指标。