Lu Zhaoyi, Deng Xiaoli, Li Hui
Department of Otolaryngology, Head and Neck Surgery, Xiangya Hospital, Central South University, Changsha, China.
Department of Otolaryngology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, China.
Front Oncol. 2020 Nov 18;10:569002. doi: 10.3389/fonc.2020.569002. eCollection 2020.
Tumor-associated macrophages (TAMs) are regarded as the most abundantly infiltrating immune cells around the tumor microenvironment (TME) in head and neck squamous cell carcinoma (HNSCC), which plays an essential role in immunosuppression and tumorigenesis. In the TCGA HNSCC cohort, 500 patients with clinical-pathological information and RNA sequence expression were randomly assigned to training for lasso regression and validation for verification, respectively. A TAM-based ten-gene signature (TBGs) was constructed, which divided the patients into high-risk and low-risk groups, could predict overall survival (OS) of HNSCC patients in the training dataset ( = 3.527e) and validation dataset ( = 3.785e). The result of Cox univariate and multivariate regression analyses showed that the risk score of TBGs could be an independent prognostic factor in HNSCC. ROC curve confirmed that the risk score of TBGs has good sensitivity and specificity for prognosis prediction (AUC = 0.659) and was also verified by the validation dataset (AUC = 0.621). We obtained key risk transcription factors (TFs)-EHF and SNAI2-by correlation analysis with TBGs. Moreover, we ran a gene set enrichment analysis (GSEA) to speculate that TBGs act on interstitial remodeling, tumor killing, metabolic reprogramming, and tumor immune-related pathways. Finally, we combined clinical-pathological features and risk score of TBGs to establish clinical nomograms, and calibration curves verified the accuracy of long-term clinical prognosis in the two datasets (C-index of 5-year OS = 0.721 and 0.716). In general, the TBGs we obtained may accurately predict the prognosis of HNSCC patients to provide personalized treatment.
肿瘤相关巨噬细胞（TAMs）被认为是头颈部鳞状细胞癌（HNSCC）肿瘤微环境（TME）中浸润最丰富的免疫细胞，在免疫抑制和肿瘤发生中起重要作用。在TCGA HNSCC队列中，500例具有临床病理信息和RNA序列表达的患者分别被随机分配用于套索回归训练和验证。构建了基于TAM的十基因特征（TBGs），将患者分为高风险和低风险组，该特征可以预测训练数据集（= 3.527e）和验证数据集（= 3.785e）中HNSCC患者的总生存期（OS）。Cox单变量和多变量回归分析结果表明，TBGs的风险评分可能是HNSCC的独立预后因素。ROC曲线证实，TBGs的风险评分对预后预测具有良好的敏感性和特异性（AUC = 0.659），并在验证数据集中也得到了验证（AUC = 0.621）。通过与TBGs的相关性分析，我们获得了关键风险转录因子（TFs）——EHF和SNAI2。此外，我们进行了基因集富集分析（GSEA），推测TBGs作用于间质重塑、肿瘤杀伤、代谢重编程和肿瘤免疫相关途径。最后，我们结合临床病理特征和TBGs的风险评分建立了临床列线图，校准曲线验证了两个数据集中长期临床预后的准确性（5年OS的C指数 = 0.721和0.716）。总体而言，我们获得的TBGs可能准确预测HNSCC患者的预后，以提供个性化治疗。
