Wang Yangyang, Zhao Shihui, Du Songtao, Xia Tianyi, Song Liqiang, Xia Mingyu, Zhang Bomiao
Department of Colorectal Surgery, Harbin Medical University Cancer Hospital, Harbin, 150081, China.
Discov Oncol. 2025 Jan 24;16(1):83. doi: 10.1007/s12672-025-01838-3.
Early diagnosis and disease management based on risk stratification have a very positive impact on colon adenocarcinoma (COAD) prognosis. It is of positive significance to further explore risk stratification of COAD patients and identify predictive molecular biomarkers. PANoptosis is defined as a form of inflammatory cell death regulated by PANoptosome, with common features of pyroptosis, apoptosis and necroptosis. The role of PANoptosis in COAD has not been fully studied. In this study, we analyzed significant differences in the expression of PANoptosis-related gene (PRG) features in COAD. Subsequently, the PANoptosis associated lncRNAs (PALs) associated with PRGs were analyzed by LASSO algorithm and multivariate Cox analysis, and PALs related to the prognosis of COAD were selected. Based on the expression patterns of prognostic PAL features, we performed unsupervised consensus cluster analysis to categorize COAD samples into distinct PAL molecular subtypes and investigate their associated immune infiltration characteristics. We subsequently constructed PAL score model based on prognostic characteristics and verified its independent prognostic value for COAD. The nomogram diagnostic model was established to confirm the prognostic value of PAL scoring system again. Pathway enrichment analysis, somatic mutation profiling, and drug sensitivity analysis were employed to comprehensively assess the clinical value of the PAL score. Additionally, qRT-PCR was used to further validate the abnormal expression of the selected targets in COAD. Our results provide a new idea for clinical risk stratification and new evidence for the role of PANoptosis in COAD.
基于风险分层的早期诊断和疾病管理对结肠腺癌（COAD）的预后具有非常积极的影响。进一步探索COAD患者的风险分层并确定预测性分子生物标志物具有积极意义。泛凋亡被定义为由泛凋亡小体调节的一种炎症性细胞死亡形式，具有焦亡、凋亡和坏死性凋亡的共同特征。泛凋亡在COAD中的作用尚未得到充分研究。在本研究中，我们分析了COAD中泛凋亡相关基因（PRG）特征表达的显著差异。随后，通过LASSO算法和多变量Cox分析对与PRG相关的泛凋亡相关lncRNAs（PAL）进行分析，并选择与COAD预后相关的PAL。基于预后PAL特征的表达模式，我们进行了无监督一致性聚类分析，将COAD样本分类为不同的PAL分子亚型，并研究其相关的免疫浸润特征。随后，我们基于预后特征构建了PAL评分模型，并验证了其对COAD的独立预后价值。建立列线图诊断模型以再次确认PAL评分系统的预后价值。采用通路富集分析、体细胞突变谱分析和药物敏感性分析来全面评估PAL评分的临床价值。此外，使用qRT-PCR进一步验证所选靶点在COAD中的异常表达。我们的结果为临床风险分层提供了新思路，并为泛凋亡在COAD中的作用提供了新证据。
