免疫相关特征确定 IL1R2 是胰腺癌的免疫学和预后生物标志物

Chengcheng Wang, Yuan Chen, Xinpeng Yin, Ruiyuan Xu, Rexiati Ruze, Jianlu Song, Chenglin Hu, Yupei Zhao
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摘要

胰腺癌是侵袭性最强的恶性肿瘤之一,因此迫切需要一个强大的预后特征和新型生物标志物来对患者进行准确分层并优化临床决策。 我们在公共数据集中应用了一系列生物信息学分析,以构建免疫相关特征。此外,还确定了该特征中最关键的基因。通过GSEA、CIBERSORT、ESTIMATE、免疫表观评分算法、单细胞分析和功能实验,揭示了核心基因功能的潜在机制。 构建并验证了免疫相关预后特征和相关提名图。在构成特征的基因中,IL1R2被确定为在风险特征中占据最重要位置的基因。同时,敲除IL1R2能显著抑制胰腺癌细胞的增殖、侵袭和迁移能力。此外,IL1R2的高表达与胰腺癌微环境中CD8+ T细胞浸润的减少有关,这可能是由于癌细胞中PD-L1的高表达所致。最后,IPS算法证明,IL1R2高表达患者的肿瘤突变负荷较高,从免疫疗法中获益的概率也较高。 总之,我们的研究构建了一个有效的免疫相关预后特征,确定了IL1R2在胰腺癌发展中的关键作用,以及其作为胰腺癌免疫治疗疗效预测生物标记物的潜力。
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Immune-related signature identifies IL1R2 as an immunological and prognostic biomarker in pancreatic cancer
Pancreatic cancer is one of the most aggressive malignancies, a robust prognostic signature and novel biomarkers are urgently needed for accurate stratification of the patients and optimization of clinical decision-making. A list of bioinformatic analysis were applied in public dataset to construct an immune-related signature. Furthermore, the most pivotal gene in the signature was identified. The potential mechanism of the core gene function was revealed through GSEA, CIBERSORT, ESTIMATE, immunophenoscore algorithm, single cell analysis and functional experiment. An immune-related prognostic signature and associated nomogram were constructed and validated. Among the genes constituting the signature, IL1R2 was identified as the gene occupying the most paramount position in the risk signature. Meanwhile, Knockdown of IL1R2 significantly inhibited the proliferation, invasion and migration ability of pancreatic cancer cells. Additionally, high IL1R2 expression was associated with reduced CD8+ T cell infiltration in pancreatic cancer microenvironment, which may be due to high PD-L1 expression in cancer cells. Finally, the IPS algorithm proved that patients with high IL1R2 expression possessed a higher tumor mutation burden and a higher probability of benefiting from immunotherapy. In conclusion, our study constructed an efficient immune-related prognostic signature and identified the key role of IL1R2 in the development of pancreatic cancer, as well as its potential to serve as a biomarker for immunotherapy efficacy prediction for pancreatic cancer.
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