School of Information Engineering, Henan University of Science and Technology, Luoyang, China.
State Key Laboratory of Esophageal Cancer Prevention and Treatment, The First Affiliated Hospital of Henan University of Science and Technology, Luoyang, China.
PeerJ. 2024 Jul 10;12:e17690. doi: 10.7717/peerj.17690. eCollection 2024.
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 cell experiments were conducted.
We screened 149 PCD-related DEGs, of which five DEGs (, , , , and ) 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. , and were overexpressed in cancer tissues and cells of ESCC. Notably, 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.
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）是细胞自我消亡的重要途径，与癌症的进展密切相关。对其机制进行详细研究可能有助于 ESCC 的治疗。
我们从公共数据库中获得 ESCC 患者的表达谱数据，并从之前的研究中获得与 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 中的枢纽基因。此外，基于 HTFtarget 和 TargetScan 数据库，选择与枢纽基因相互作用的转录因子（TFs）和 miRNA。使用 CIBERSORT 算法分析枢纽基因与免疫细胞的关系。最后，通过一系列细胞实验验证筛选出的枢纽基因对 ESCC 发生和发展的潜在影响。
我们筛选出 149 个与 PCD 相关的差异表达基因，其中 5 个差异表达基因（、、、、和）被鉴定为 ESCC 的枢纽基因。使用枢纽基因构建的综合模型的接收者操作特征（ROC）曲线下面积（AUC）达到 0.997，显示出较高的诊断准确性。调节枢纽基因的 TF 和 miRNA 的数量分别为 105 个和 22 个。在 ESCC 的癌组织和细胞中，、和过度表达。值得注意的是，下调可抑制 ESCC 细胞迁移和侵袭，并改变重要凋亡和存活蛋白的表达。
本研究鉴定出了具有较高诊断准确性的 ESCC 潜在标志物，为 ESCC 的研究提供了新的视角和实验基础。
