食管鳞状细胞癌（ESCC）是一种致命的食管癌。程序性细胞死亡（PCD）是细胞自我毁灭的重要途径，与癌症进展密切相关。对其机制的详细研究可能有助于ESCC的治疗。我们从公共数据库中获得了ESCC患者的表达谱数据，并从以往的研究中获得了与12种PCD相关的基因。应用差异表达分析、机器学习分析、线性支持向量机（SVM）、随机森林和最小绝对收缩和选择算子（LASSO）回归分析从 PCD 相关基因中筛选 ESCC 中的 Hub 基因。此外，基于HTFtarget和TargetScan数据库，选择了与hub基因相互作用的转录因子（TF）和miRNA。使用CIBERSORT算法分析hub基因与免疫细胞之间的关系。最后，为了验证筛选的hub基因对ESCC发生发展的潜在影响，我们进行了一系列体外细胞实验。我们筛选了149个PCD相关DEG，其中5个DEG（INHBA、LRRK2、HSP90AA1、HSPB8和EIF2AK2）被确定为食管鳞癌的枢纽基因。利用hub基因开发的集成模型的受试者工作特征（ROC）曲线下面积（AUC）达到0.997，显示出极高的诊断准确性。调节hub基因的TF和miRNA的数量分别为105和22。 INHBA、HSP90AA1和EIF2AK2在食管鳞癌组织和细胞中过表达。值得注意的是，INHBA敲低抑制了ECSS细胞的迁移和侵袭，并改变了重要的凋亡和存活蛋白的表达。本研究鉴定了对ESCC诊断具有良好准确性的重要分子，这可能为ESCC研究提供新的视角和实验基础。©2024陈等人。

Esophageal squamous cell carcinoma (ESCC) is a deadly type of esophageal cancer. Programmed cell death (PCD) is an important pathway of cellular self-extermination and is closely involved in cancer progression. A detailed study of its mechanism may contribute to ESCC treatment.We obtained expression profiling data of ESCC patients from public databases and genes related to 12 types of PCD from previous studies. Hub genes in ESCC were screened from PCD-related genes applying differential expression analysis, machine learning analysis, linear support vector machine (SVM), random forest and Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis. In addition, based on the HTFtarget and TargetScan databases, transcription factors (TFs) and miRNAs interacting with the hub genes were selected. The relationship between hub genes and immune cells were analyzed using the CIBERSORT algorithm. Finally, to verify the potential impact of the screened hub genes on ESCC occurrence and development, a series of in vitro cell experiments were conducted.We screened 149 PCD-related DEGs, of which five DEGs (INHBA, LRRK2, HSP90AA1, HSPB8, and EIF2AK2) were identified as the hub genes of ESCC. The area under the curve (AUC) of receiver operating characteristic (ROC) curve of the integrated model developed using the hub genes reached 0.997, showing a noticeably high diagnostic accuracy. The number of TFs and miRNAs regulating hub genes was 105 and 22, respectively. INHBA, HSP90AA1 and EIF2AK2 were overexpressed in cancer tissues and cells of ESCC. Notably, INHBA knockdown suppressed ECSS cell migration and invasion and altered the expression of important apoptotic and survival proteins.This study identified significant molecules with promising accuracy for the diagnosis of ESCC, which may provide a new perspective and experimental basis for ESCC research.©2024 Chen et al.