Zhu Wenying, Ye Zhipeng, Chen Ling, Liang Haifeng, Cai Qian
Department of Otolaryngology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.
Department of Medical Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China.
Int Immunopharmacol. 2021 Dec;101(Pt B):108268. doi: 10.1016/j.intimp.2021.108268. Epub 2021 Oct 20.
Pyroptosis, a type of regulated cell death controlled by the gasdermin family of proteins to form plasma membrane pores is known. Nonetheless, the function of pyroptosis-related long non-coding RNAs (lncRNAs) in this process still lacks exhaustive elucidation in head and neck squamous cell carcinoma (HNSCC). Other attributes encompassing the function of such lncRNAs in the immune microenvironment and potential prognosis for HNSCC are yet to see the light of the day. This work was designed to probe the possible prognostic worth of pyroptosis-related lncRNAs along with their impact on the immune microenvironment in the case of HNSCC.
The Cancer Genome Atlas (TCGA) database was the source of RNA-sequencing data of HNSCC patients. Pearson correlation analysis was employed to scour for lncRNAs linked to pyroptosis based on 40 genes related to the process. Following the construction of a pyroptosis-related lncRNA signature employing univariate, Least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression analyses, survival and nomogram analyses ensued to scrutinize the predictive value of the prognostic signature.
The segregation of patients into two risk groups was done by the constructed pyroptosis-related-lncRNA signature (encompassing 14 lncRNAs). The prognosis was poorer for individuals of the high-risk group versus (vs.) the low-risk group with the risk score emerging as an independent prognostic factor by regression analyses. The accuracy of this signature was corroborated by Receiver operating characteristic curve (ROC) analysis with the three-years area under time-dependent ROC curve (AUC) reaching 0.767. Further analyses unveiled a conspicuous enrichment of immune-related pathways in the low-risk group. The high-risk group demonstrated an immunologically "cold" profile based on the immune cell infiltration landscape.
The lncRNA signature encompassing 14 pyroptosis-related lncRNAs could be a prognostic marker for HNSCC, suggesting pyroptosis might be a promising therapeutic target in HNSCC.
焦亡是一种由gasdermin家族蛋白控制以形成质膜孔的程序性细胞死亡。然而，焦亡相关长链非编码RNA（lncRNA）在此过程中的功能在头颈部鳞状细胞癌（HNSCC）中仍缺乏详尽的阐释。这些lncRNA在免疫微环境中的功能以及对HNSCC的潜在预后等其他特性仍未被揭示。本研究旨在探讨焦亡相关lncRNA在HNSCC中的可能预后价值及其对免疫微环境的影响。
癌症基因组图谱（TCGA）数据库是HNSCC患者RNA测序数据的来源。基于40个与焦亡相关的基因，采用Pearson相关性分析来寻找与焦亡相关的lncRNA。在构建焦亡相关lncRNA特征后，进行单变量、最小绝对收缩和选择算子（LASSO）以及多变量Cox回归分析，随后进行生存分析和列线图分析，以检验预后特征的预测价值。
通过构建的焦亡相关lncRNA特征（包含14个lncRNA）将患者分为两个风险组。高危组个体的预后比低危组差，风险评分经回归分析成为独立的预后因素。受试者工作特征曲线（ROC）分析证实了该特征的准确性，三年时间依赖ROC曲线下面积（AUC）达到0.767。进一步分析发现低风险组中免疫相关通路显著富集。基于免疫细胞浸润情况，高风险组呈现出免疫“冷”状态。
包含14个焦亡相关lncRNA的lncRNA特征可能是HNSCC的预后标志物，提示焦亡可能是HNSCC中一个有前景的治疗靶点。
