Identification of PANoptosis associated lncRNAs associated with clinical prognosis and immune infiltration microenvironment in colon adenocarcinoma.

IF 2.9 4区 医学 Q3 ENDOCRINOLOGY & METABOLISM Discover. Oncology Pub Date : 2025-01-24 DOI:10.1007/s12672-025-01838-3
Yangyang Wang, Shihui Zhao, Songtao Du, Tianyi Xia, Liqiang Song, Mingyu Xia, Bomiao Zhang
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Abstract

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.

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结肠腺癌PANoptosis相关lncrna与临床预后及免疫浸润微环境的关系
基于风险分层的早期诊断和疾病管理对结肠腺癌(COAD)预后有非常积极的影响。这对进一步探讨COAD患者的风险分层,寻找具有预测意义的分子生物标志物具有积极意义。PANoptosis是由PANoptosome调控的炎症细胞死亡的一种形式,具有焦亡、凋亡和坏死坏死的共同特征。PANoptosis在COAD中的作用尚未得到充分的研究。在本研究中,我们分析了COAD中panoptosis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分析与PRGs相关的PANoptosis相关lncRNAs (PALs),筛选出与COAD预后相关的PALs。基于预后PAL特征的表达模式,我们进行了无监督共识聚类分析,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。我们随后基于预后特征构建PAL评分模型,并验证其对COAD的独立预测价值。建立nomogram诊断模型,再次验证PAL评分系统的预后价值。通过途径富集分析、体细胞突变谱分析和药物敏感性分析,综合评价PAL评分的临床价值。此外,利用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的思路,并为PANoptosis在COAD中的作用提供了新的证据。
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来源期刊
Discover. Oncology
Discover. Oncology Medicine-Endocrinology, Diabetes and Metabolism
CiteScore
2.40
自引率
9.10%
发文量
122
审稿时长
5 weeks
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