Zhu Lin, Liang Feng, Han Xue, Ye Bin, Xue Lei
Department of Oncology, The Affiliated Suqian First People's Hospital of Nanjing Medical University, Suqian, China.
Department of Gastroenterology, Huai'an Second People's Hospital, The Affiliated Huai'an Hospital of Xuzhou Medical University, Huai'an, China.
J Cell Mol Med. 2025 Mar;29(6):e70434. doi: 10.1111/jcmm.70434.
Using machine learning approaches, we developed and validated a novel prognostic model for oesophageal squamous cell carcinoma (ESCC) based on glycolipid metabolism-related genes. Through integrated analysis of TCGA and GEO datasets, we established a robust 15-gene signature that effectively stratified patients into distinct risk groups. This signature demonstrated superior prognostic value and revealed significant associations with immune infiltration patterns. High-risk patients exhibited reduced immune cell infiltration, particularly in B cells and NK cells, alongside increased tumour purity. Single-cell RNA sequencing analysis uncovered unique cellular composition patterns and enhanced interaction intensities in the high-risk group, especially within epithelial and smooth muscle cells. Functional validation confirmed MECP2 as a promising therapeutic target, with its knockdown significantly inhibiting tumour progression both in vitro and in vivo. Drug sensitivity analysis identified specific therapeutic agents showing potential efficacy for high-risk patients. Our study provides both a practical prognostic tool and novel insights into the relationship between glycolipid metabolism and tumour immunity in ESCC, offering potential strategies for personalised treatment.
利用机器学习方法，我们开发并验证了一种基于糖脂代谢相关基因的新型食管鳞状细胞癌（ESCC）预后模型。通过对TCGA和GEO数据集的综合分析，我们建立了一个强大的15基因特征，可有效地将患者分层为不同的风险组。该特征显示出卓越的预后价值，并揭示了与免疫浸润模式的显著关联。高危患者的免疫细胞浸润减少，尤其是B细胞和NK细胞，同时肿瘤纯度增加。单细胞RNA测序分析揭示了高危组独特的细胞组成模式和增强的相互作用强度，特别是在上皮和平滑肌细胞内。功能验证证实MECP2是一个有前景的治疗靶点，其敲低在体外和体内均显著抑制肿瘤进展。药物敏感性分析确定了对高危患者显示出潜在疗效的特定治疗药物。我们的研究既提供了一种实用的预后工具，也为ESCC中糖脂代谢与肿瘤免疫之间的关系提供了新的见解，为个性化治疗提供了潜在策略。
