Department of Radiation Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangzhou, P.R. China.
Department of Urology, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, P.R. China.
Clin Cancer Res. 2021 Jan 1;27(1):330-341. doi: 10.1158/1078-0432.CCR-20-2166. Epub 2020 Oct 23.
To construct an immune-related gene prognostic index (IRGPI) for head and neck squamous cell carcinoma (HNSCC) and clarify the molecular and immune characteristics and the benefit of immune checkpoint inhibitor (ICI) therapy in IRGPI-defined subgroups of HNSCC.
On the basis of The Cancer Genome Atlas HNSCC immune dataset ( = 546), 22 immune-related hub genes were identified by weighted gene coexpression network analysis. Three genes were identified to construct an IRGPI by using the Cox regression method and validated with the Gene Expression Omnibus (GEO) dataset ( = 270). Afterward, the molecular and immune characteristics and the benefit of ICI therapy in IRGPI-defined subgroups were analyzed.
The IRGPI was constructed on the basis of , , and genes. IRGPI-high patients had a better overall survival than IRGPI-low patients, consistent with the results in the GEO cohort. The comprehensive results showed that a high IRGPI score was correlated with DNA repair-related pathways; low mutation rate; high infiltration of CD8 T cells, CD4 T cells, and M1 macrophages; active immunity and less aggressive phenotypes; and more benefit from ICI therapy. In contrast, a low IRGPI score was associated with cancer and metastasis-related pathways; high and mutation rate; high infiltration of B cells, M0 macrophages, and M2 macrophages; suppressive immunity and more aggressive phenotypes; and less benefit from ICI therapy.
IRGPI is a promising biomarker to distinguish the prognosis, the molecular and immune characteristics, and the immune benefit from ICI therapy in HNSCC.
构建头颈部鳞状细胞癌（HNSCC）的免疫相关基因预后指数（IRGPI），并阐明IRGPI 定义的 HNSCC 亚组中分子和免疫特征以及免疫检查点抑制剂（ICI）治疗的获益。
基于癌症基因组图谱 HNSCC 免疫数据集（n=546），通过加权基因共表达网络分析鉴定出 22 个免疫相关枢纽基因。采用 Cox 回归方法并结合基因表达综合数据库（GEO）数据集（n=270）鉴定出 3 个基因来构建 IRGPI。随后，分析了 IRGPI 定义的亚组中的分子和免疫特征以及 ICI 治疗的获益。
基于、和基因构建了 IRGPI。IRGPI 高患者的总生存率优于 IRGPI 低患者，与 GEO 队列的结果一致。综合结果表明，高 IRGPI 评分与 DNA 修复相关途径相关；低 突变率；高水平的 CD8 T 细胞、CD4 T 细胞和 M1 巨噬细胞浸润；活跃的免疫和侵袭性较低的表型；以及从 ICI 治疗中获益更多。相比之下，低 IRGPI 评分与癌症和转移相关途径相关；高 和 突变率；高水平的 B 细胞、M0 巨噬细胞和 M2 巨噬细胞浸润；抑制性免疫和侵袭性更高的表型；以及从 ICI 治疗中获益较少。
IRGPI 是一种有前途的生物标志物，可以区分 HNSCC 的预后、分子和免疫特征以及从 ICI 治疗中获益的情况。
