Huang Weicheng, Liu Yuchen, Liu Ruyi, Feng Chi, Wu Jiehua, Sun Xing, Zhu Pengfei, Chen Pengxiang, Cheng Yufeng
Department of Radiation Oncology, Qilu Hospital of Shandong University, Jinan, China.
Neutron Medical Center, Qilu Hospital of Shandong University, Jinan, China.
Front Immunol. 2025 Aug 14;16:1591252. doi: 10.3389/fimmu.2025.1591252. eCollection 2025.
Given the high incidence and mortality rates of gastrointestinal (GI) cancer, along with the lack of effective prognostic markers, this study aimed to construct a prognostic signature to identify high-risk patients facilitate precision medicine, and ultimately improve patient outcomes.
We analyzed transcriptomic data for COAD, ESCA, READ, and STAD from the TCGA and GTEx databases. Using co-expression analysis, Cox regression, and least absolute shrinkage and selection operator (LASSO) regression, we developed a necroptosis-related lncRNA signature, termed the Necro-lnc score. The predictive performance of the score was validated and assessed through survival analysis, receiver operating characteristic (ROC) analysis, and Cox regression analysis. Additionally, we conducted gene set enrichment analysis (GSEA), immune landscape profiling, and drug sensitivity prediction based on half-maximal inhibitory concentration (IC50) values. The robustness of the score was further supported by cluster analysis, and the biological functions of the selected lncRNAs were experimentally validated through phenotypic assays.
We constructed a prognostic signature comprising five necroptosis-related lncRNAs, referred to as the Necro-lnc score. Calibration plots and areas under the ROC curves (AUCs) confirmed the strong prognostic predictive capability of the score. Kaplan-Meier (K-M) survival curves revealed a significant correlation between the Necro-lnc score and patient outcomes, with high-score patients exhibiting markedly poorer prognoses. Immune landscape and drug susceptibility analyses indicated that the high-score group was characterized by hot tumors and showed greater sensitivity to immunotherapeutic drugs and targeted drugs, while the low-score group associated with cold tumors, was more responsive to chemotherapeutic agents. Furthermore, phenotypic assays demonstrated that the lncRNAs included in the Necro-lnc score play critical roles in the progression and metastasis of GI cancer.
This study developed the promising Necro-lnc score, which demonstrates potential for predicting prognosis and distinguishing between cold and hot tumors, thereby improving personalized treatment strategies for patients with GI cancer.
鉴于胃肠道（GI）癌的高发病率和死亡率，以及缺乏有效的预后标志物，本研究旨在构建一种预后特征，以识别高危患者，促进精准医学，并最终改善患者预后。
我们分析了来自TCGA和GTEx数据库的COAD、ESCA、READ和STAD的转录组数据。通过共表达分析、Cox回归和最小绝对收缩和选择算子（LASSO）回归，我们开发了一种与坏死性凋亡相关的lncRNA特征，称为Necro-lnc评分。通过生存分析、受试者工作特征（ROC）分析和Cox回归分析对该评分的预测性能进行了验证和评估。此外，我们基于半数最大抑制浓度（IC50）值进行了基因集富集分析（GSEA）、免疫景观分析和药物敏感性预测。聚类分析进一步支持了该评分的稳健性，并通过表型分析对所选lncRNAs的生物学功能进行了实验验证。
我们构建了一个由五个与坏死性凋亡相关的lncRNAs组成的预后特征，称为Necro-lnc评分。校准图和ROC曲线下面积（AUC）证实了该评分具有强大的预后预测能力。Kaplan-Meier（K-M）生存曲线显示Necro-lnc评分与患者预后之间存在显著相关性，高分患者的预后明显较差。免疫景观和药物敏感性分析表明，高分组的特征是热肿瘤，对免疫治疗药物和靶向药物表现出更高的敏感性，而低分组与冷肿瘤相关，对化疗药物更敏感。此外，表型分析表明，Necro-lnc评分中包含的lncRNAs在胃肠道癌的进展和转移中起关键作用。
本研究开发了有前景的Necro-lnc评分，该评分在预测预后和区分冷肿瘤和热肿瘤方面具有潜力，从而改善胃肠道癌患者的个性化治疗策略。
