肿瘤突变负荷在头颈部鳞癌中的预后价值

Prognostic Value of Tumor Mutational Burden in Head and Neck Squamous Cell Carcinoma

目的:研究头颈部鳞状细胞癌中肿瘤突变负荷(tumor mutational burden,TMB)的水平及预后价值。方法:收集肿瘤与癌症基因组图谱中头颈部鳞状细胞癌数据集的临床资料和基因表达谱数据。利用生物信息学方法,根据体细胞突变数据计算TMB。采用Cox回归模型评价肿瘤突变负荷与总生存率(overall survival,OS)的关系。结果:TMB水平范围为0.1~95.9 mutations/Mb。多因素logistic回归分析显示TMB水平与肿瘤病变亚部位显著相关。Kaplan-Meier分析显示高TMB患者组的OS显著降低(P=0.007)。亚组分析显示口腔癌患者高TMB与低OS相关(P=0.004);在口咽癌、下咽癌和喉癌患者中,高TMB组和低TMB组的生存率差异无统计学意义。经混杂因素校正后的多因素分析显示,TMB是头颈部鳞状细胞癌患者OS的独立预后因素(P=0.022,危险比:1.416,95%可信区间:1.052~1.907)。结论:TMB是影响头颈部鳞癌患者生存的独立预后因素。高TMB值能识别出预后差的患者,他们可能受益于免疫检查点抑制剂治疗。

Objective:To investigates the level and prognostic value of tumor mutational burden(TMB)in head and neck squamous cell carcinoma(HNSCC).Methods:Clinical information and gene expression profiles from the Cancer Genome Altas-HNSCC dataset were retrospectively collected.TMB levels were calculated basis on data of somatic mutations by using bioinformatics methods.Cox regression model was performed to evaluate the association between TMB and overall survival(OS).Results:The TMB level ranged from 0.053-95.868 mutations/Mb.Multivariate logistic regression analysis showed that TMB was significantly related to sublesional sites.Kaplan-Meier analysis showed a significant reduction in OS in patients with high TMB(P=0.007).Subgroup analyses revealed that high TMB was associated with poorer OS in patients with oral cancer(P=0.004).No significant differences in survival were observed between high and low TMB groups in patients with oropharyngeal cancer,hypopharyngeal cancer and laryngeal cancer.Multivariate analysis(confounding factors adjusted)revealed TMB was an independent prognostic factor for OS in HNSCC patients(P=0.022,hazard ratio:1.416,95%confidence interval:1.052-1.907).Conclusion:TMB is an independent prognostic factor for the survival of patients with HNSCC.High TMB can identify patients with poor outcome who might benefit from immune checkpoint inhibitors.