Department of Radiology, The First Hospital of Qinhuangdao, Qinhuangdao, Hebei, China.
Medicine (Baltimore). 2024 Aug 2;103(31):e39184. doi: 10.1097/MD.0000000000039184.
Increasing evidence has shown that hypoxia is a biomarker of tumor proliferation and metastasis. This research aimed to identify a hypoxia-associated gene prognostic index (HAGPI) in head and neck squamous cell carcinoma (HNSCC) and based on HAGPI-defined subgroups to predict prognosis and response to immune checkpoint inhibitors therapy.
RNA-sequencing transcriptomic data for patients with HNSCC were downloaded from The Cancer Genome Atlas (TCGA). Protein-protein interaction network analysis was performed to select hypoxia-related hub genes. Univariate and multivariate cox regression analyses were used to identify hub genes to develop the HAGPI. Afterward expression data were imported into CIBERSORT to evaluate the relative proportion of 22 immune cells and compared the relative proportions of immune cells between the 2 HAGPI subgroups. The relationship between immunopheno score (IPS) and HAGPI was validated for immune checkpoint inhibitors (ICIs) response in TCGA cohorts.
The HAGPI was constructed based on HS3ST1, HK1, PGK1, STC2, SERPINE1, PKLR genes. In high-HAGPI patients, the primary and secondary endpoint events in TCGA and GEO cohorts were significantly lower than low-HAGPI groups (P < .05). HAGPI-high patients exhibited a poorer prognosis than HAGPI-low patients did. The abundance of M2 macrophages and NK cell were significantly enhanced in the high-HAGPI while T cells regulatory and T cells CD8, were markedly elevated in the low-HAGPI. Meanwhile, patients in the low-HAGPI patients had higher levels of immunosuppressant expression and less aggressive phenotypes. Furthermore, IPS analysis showed that the low-HAGPI group with higher IPS represented a more immunogenic phenotype.
The current study developed and verified a HAPGI model that can be considered as an independent prognostic biomarker and elucidated the tumor immune microenvironment of HNSCC.
越来越多的证据表明，缺氧是肿瘤增殖和转移的生物标志物。本研究旨在鉴定头颈部鳞状细胞癌（HNSCC）中与缺氧相关的基因预后指数（HAGPI），并基于 HAGPI 定义的亚组预测预后和对免疫检查点抑制剂治疗的反应。
从癌症基因组图谱（TCGA）下载 HNSCC 患者的 RNA-seq 转录组数据。进行蛋白质-蛋白质相互作用网络分析以选择与缺氧相关的枢纽基因。使用单变量和多变量 Cox 回归分析鉴定枢纽基因以开发 HAGPI。之后将表达数据导入 CIBERSORT 以评估 22 种免疫细胞的相对比例，并比较 2 个 HAGPI 亚组之间免疫细胞的相对比例。验证免疫表型评分（IPS）与 HAGPI 之间的关系，以预测 TCGA 队列中免疫检查点抑制剂（ICIs）的反应。
基于 HS3ST1、HK1、PGK1、STC2、SERPINE1 和 PKLR 基因构建了 HAGPI。在 TCGA 和 GEO 队列中，高 HAGPI 患者的主要和次要终点事件明显低于低 HAGPI 组（P <.05）。HAGPI 高患者的预后明显差于 HAGPI 低患者。高 HAGPI 组中 M2 巨噬细胞和 NK 细胞的丰度显著增加，而低 HAGPI 组中 T 细胞调节和 T 细胞 CD8 的丰度显著升高。同时，低 HAGPI 组患者的免疫抑制剂表达水平较高，侵袭性表型较少。此外，IPS 分析表明，低 HAGPI 组中具有更高 IPS 的患者具有更具免疫原性的表型。
本研究开发并验证了 HAPGI 模型，可作为独立的预后生物标志物，并阐明了 HNSCC 的肿瘤免疫微环境。
