Clinical Medical College, Dali University, Dali, 671000, Yunnan, China.
Department of Otolaryngology, The First Affiliated Hospital of Dali University, Dali, 671000, Yunnan, China.
Eur Arch Otorhinolaryngol. 2021 Oct;278(10):3973-3983. doi: 10.1007/s00405-020-06580-w. Epub 2021 Jan 15.
Head and neck squamous cell carcinoma (HNSCC) are a highly aggressive tumor with an extremely poor prognosis. Thus, we aimed to develop and validate a robust prognostic signature that can estimate the prognosis for HNSCC.
Data on gene expressions and clinical were downloaded from TCGA and GEO database. To develop the best prognosis signature, a LASSO Cox Regression model was employed. Time-dependent receiver-operating characteristic (ROC) was used to determine the best cut-off value. Patients were divided into high-risk and low-risk hypoxia groups according to cut-off value. Survival differences were evaluated by log-rank test, while multivariate analysis was performed by a Cox proportional hazards model.
A 17-HRGPs composed of 24 unique genes was constructed, which was significantly related to OS. In the TCGA and GEO datasets, patients in the high hypoxia risk group have a poor prognosis (TCGA: P < 0.001, GEO: P < 0.05). After adjusting for other clinicopathological parameters, the 17-HRGP signature was independent prognostic factors in patients with HNSCC (P < 0.05). Functional analysis revealed that mRNA binding, gene silencing by RNA, RNA binding involved in posttranscriptional gene silencing signaling pathway were enriched in the low-risk groups. For this model, C-index was 0.684, which was higher than that of many established risk models. Macrophages M0, Mast cells activated, NK cells resting, T cells CD4 memory resting, etc. were significantly higher in the high-risk group, and B cells memory, Plasma cells, T cells follicular helper, T cells gamma delta, T cells CD8, etc. were significantly higher in the low-risk group.
In summary, our study constructed a robust HRGPs signature as molecular markers for predicting the outcome of HNSCC patients.
头颈部鳞状细胞癌（HNSCC）是一种侵袭性极强、预后极差的肿瘤。因此，我们旨在开发和验证一种稳健的预后标志物，以评估 HNSCC 的预后。
从 TCGA 和 GEO 数据库下载基因表达和临床数据。为了开发最佳的预后标志物，采用 LASSO Cox 回归模型。采用时间依赖性接收器工作特征（ROC）确定最佳截断值。根据截断值将患者分为高风险和低风险缺氧组。通过对数秩检验评估生存差异，通过 Cox 比例风险模型进行多变量分析。
构建了一个由 24 个独特基因组成的 17-HRGP 组成的预后标志物，与 OS 显著相关。在 TCGA 和 GEO 数据集，高缺氧风险组患者预后较差（TCGA：P<0.001，GEO：P<0.05）。在调整其他临床病理参数后，17-HRGP 标志物是 HNSCC 患者的独立预后因素（P<0.05）。功能分析显示，低风险组中富含 mRNA 结合、基因沉默 RNA、RNA 结合参与转录后基因沉默信号通路。该模型的 C 指数为 0.684，高于许多已建立的风险模型。高风险组中巨噬细胞 M0、激活的肥大细胞、静止的 NK 细胞等明显升高，低风险组中 B 细胞记忆、浆细胞、滤泡辅助性 T 细胞、γδT 细胞、CD8+T 细胞等明显升高。
综上所述，我们的研究构建了一个稳健的 HRGPs 标志物，作为预测 HNSCC 患者预后的分子标志物。
