肺鳞状细胞癌中焦亡相关预后特征与免疫浸润的综合分析。
Integrative Analysis of Pyroptosis-Related Prognostic Signature and Immunological Infiltration in Lung Squamous Cell Carcinoma.
机构信息
Department of Oncology, The Central Hospital of Yongzhou, No. 396 Yiyun Road, Yongzhou City, 425000 Hunan Province, China.
出版信息
Biomed Res Int. 2022 Jun 1;2022:4944758. doi: 10.1155/2022/4944758. eCollection 2022.
BACKGROUND
Lung cancer is one of leading causes of human health threatening with approximately 2.09 million initially diagnosed cases and 1.76 million deaths worldwide annually. Pyroptosis is a programmed cell death mediated by Gasdermin family proteins. Pyroptosis could suppress the tumor oncogenesis and progression; nevertheless, pyroptosis could promote tumor growth by forming a suitable microenvironment.
METHODS
LASSO Cox regression analysis was performed to construct prognostic pyroptosis-related gene (PRG) signature. A ceRNA was constructed to explore the potential lncRNA-miRNA-mRNA regulatory axis in LUSC.
RESULTS
The expression of 26 PRGs were increased or decreased in LUSC. We also summarized simple nucleotide variation and copy number variation landscape of PRGs in LUSC. Prognosis analysis suggested a poor overall survival rate in LUSC patients with high expression of IL6, IL1B, ELANE, and CASP6. A pyroptosis-related prognostic signature was developed based on four prognostic PRGs. High-risk score LUSC patients had a poor overall survival rate versus low-risk score patients with an AUC of 0.565, 0.641, and 0.619 in 1-year, 3-year, and 5-year ROC curves, respectively. Moreover, the risk score was correlated with immune infiltration in LUSC. Further analysis revealed that pyroptosis-related prognostic signature was correlated with immune cell infiltration, tumor mutation burden, microsatellite instability, and drug sensitivity. We also constructed a ceRNA network and identified a lncRNA KCNQ1OT1/miR-328-3p/IL1B regulatory axis for LUSC.
CONCLUSION
A bioinformatics method was performed to develop a pyroptosis-related prognostic signature containing four genes (IL6, IL1B, ELANE, and CASP4) in LUSC. We also constructed a ceRNA network and identified a lncRNA KCNQ1OT1/miR-328-3p/IL1B regulatory axis for LUSC. Further in vivo and in vitro studies should be conducted to verify these results.
背景
肺癌是威胁人类健康的主要原因之一，全球每年约有 209 万例初诊病例和 176 万例死亡病例。细胞焦亡是一种由 GSDM 家族蛋白介导的程序性细胞死亡。细胞焦亡可以抑制肿瘤的发生和进展；然而，细胞焦亡也可以通过形成适宜的微环境促进肿瘤生长。
方法
使用 LASSO Cox 回归分析构建预后相关的细胞焦亡基因（PRG）特征。构建 ceRNA 以探讨 LUSC 中潜在的长非编码 RNA-miRNA-mRNA 调控轴。
结果
在 LUSC 中，26 个 PRG 的表达升高或降低。我们还总结了 LUSC 中 PRG 的简单核苷酸变异和拷贝数变异景观。预后分析表明，IL6、IL1B、ELANE 和 CASP6 高表达的 LUSC 患者总生存率较低。基于四个预后 PRG 构建了细胞焦亡相关的预后特征。高风险评分的 LUSC 患者总生存率低于低风险评分患者，1 年、3 年和 5 年 ROC 曲线的 AUC 分别为 0.565、0.641 和 0.619。此外，风险评分与 LUSC 中的免疫浸润相关。进一步分析表明，细胞焦亡相关的预后特征与免疫细胞浸润、肿瘤突变负荷、微卫星不稳定和药物敏感性相关。我们还构建了 ceRNA 网络，鉴定了 LUSC 中的 lncRNA KCNQ1OT1/miR-328-3p/IL1B 调控轴。
结论
本研究采用生物信息学方法构建了一个包含四个基因（IL6、IL1B、ELANE 和 CASP4）的细胞焦亡相关预后特征，构建了 ceRNA 网络，鉴定了 LUSC 中的 lncRNA KCNQ1OT1/miR-328-3p/IL1B 调控轴。需要进一步进行体内和体外研究来验证这些结果。
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