基于转录组分析的食管鳞状细胞癌性别相关预后基因的筛选和验证

Screening and Validation of Gender-Related Prognostic Genes in Esophageal Squamous Cell Carcinoma Based on Transcriptomic Analysis

摘要: 目的：基于转录组分析筛选食管鳞状细胞癌(Esophageal Squamous Cell Carcinoma, ESCC)性别相关预后基因(Gender-Related Prognostic Genes, GRPGs)，开发风险评分模型及预后列线图，临床样本验证关键基因的生物学特征。方法：GSE53625数据集中，加权基因共表达网络分析(Weighted Gene Co-expression Network Analysis, WGCNA)筛选性别相关模块基因，与Kaplan-Meier (K-M)分析得到的预后基因取交集。最小绝对收缩与选择算子(Least Absolute Shrinkage and Selection Operator, LASSO)及多变量Cox回归分析方法识别GRPGs。构建风险评分模型，并将独立预后因素纳入预后预测列线图。校准曲线、受试者工作特征曲线(Receiver Operating Characteristic, ROC)和决策曲线分析(Decision Curve Analysis, DCA)评估模型临床应用效能。结果：风险评分将患者分为高风险组和低风险组，两组总生存期(Overall Survival, OS)有显著差异。涵盖年龄、治疗方式和风险评分的预后列线图显示出良好的校准和鉴别能力。免疫组织化学分析(Immunohistochemistry, IHC)显示女性患者IL5RA表达显著升高，其表达水平与免疫调控及雌激素代谢相关通路的活性正相关。结论：本研究鉴定出的GRPGs有望成为新型预后生物标志物，为ESCC的精准治疗及预后评估提供重要参考依据。

Abstract: Aims: To identify gender-related prognostic genes (GRPGs) in esophageal squamous cell carcinoma (ESCC) through transcriptome analysis, develop a risk scoring model and prognostic nomogram, and validate the biological characteristics of key genes in clinical samples. Methods: Weighted gene co-expression network analysis (WGCNA) was applied to identify gender-associated module genes from the GSE53625 dataset, which intersected with prognostic genes derived from Kaplan-Meier (K-M) survival analysis. Least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression analyses were applied to identify Gender-Related Prognostic Genes (GRPGs). We constructed a risk score model and incorporated independent prognostic factors into a nomogram to predict ESCC patient outcomes. Calibration curves, receiver operating characteristic (ROC) curves, and decision curve analysis (DCA) evaluated the clinical utility of the model. Results: The risk model stratified patients into high- and low-risk groups with significantly different overall survival (OS). The prognostic model, which integrates age, treatment modality, and risk score, exhibited excellent calibration and discriminative ability. Immunohistochemistry (IHC) revealed elevated IL5RA expression in female patients, positively correlating with activity in immune regulation and estrogen metabolism pathways. Conclusion: The identified GRPGs demonstrate potential as novel prognostic biomarkers, providing a critical foundation for precision therapy and survival assessment in ESCC.