Identification of pyroptosis-related clusters for prediction of overall survival and characterization of tumor microenvironment infiltration in laryngeal squamous cell carcinoma

Wei Du, Xueming Xia, Jiayun Yu, Bin Shao
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Abstract

Laryngeal squamous cell carcinoma (LSCC) accounts for one-third of head and neck squamous carcinoma (HNSCC). Although improvements have been made in treatments, the prognosis of patients with LSCC is unsatisfactory. Pyroptosis creates an environment that inhibits tumor growth in various cancers, but pyroptosis regulation in the tumor immune microenvironment in LSCC remains little known. The Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases were used to collect clinical traits and gene expression data of LSCC patients. We present a systematic overview of the immune microenvironment of LSCC based on genetics and transcriptional profiles of pyroptosis-related genes (PRGs) and divide 220 LSCC into three distinct PRGclusters. Based on the three survival-related PRGs identified in Lasso-penalized Cox regression, samples from the training and validation cohorts were divided into two discrete geneClusters. We construct a prognostic model based on Risk score, quantify pyroptosis level and link it with patient outcome. Furthermore, we verified the expression level of one prognostic gene Basic Leucine Zipper ATF-Like Transcription Factor at the tissue level in the validation experiment. These findings reveal the crucial role of pyroptosis and can assist in predicting patient prognosis, guiding optimal treatment choices, and developing new immunotherapies for LSCC.

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用于预测喉鳞状细胞癌总生存率的焦下垂相关簇的鉴定和肿瘤微环境浸润的表征
喉鳞状细胞癌(LSCC)占头颈部鳞状细胞癌的三分之一。尽管治疗有所改善,但LSCC患者的预后并不令人满意。Pyroptosis在各种癌症中创造了一种抑制肿瘤生长的环境,但LSCC中肿瘤免疫微环境中的Pyroptosi调节仍鲜为人知。利用基因表达综合数据库(GEO)和癌症基因组图谱(TCGA)数据库收集LSCC患者的临床特征和基因表达数据。基于pyroptosis相关基因(PRG)的遗传学和转录谱,我们对LSCC的免疫微环境进行了系统综述,并将220个LSCC分为三个不同的PRG簇。基于Lasso惩罚Cox回归中确定的三个与生存相关的PRG,将来自训练和验证队列的样本分为两个离散的基因簇。我们构建了一个基于风险评分的预后模型,量化焦下垂水平,并将其与患者结果联系起来。此外,我们在验证实验中验证了一种预后基因碱性亮氨酸拉链ATF样转录因子在组织水平上的表达水平。这些发现揭示了pyroptosis的关键作用,有助于预测患者预后,指导最佳治疗选择,并开发新的LSCC免疫疗法。
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