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基于胀亡相关长非编码 RNA 的算法构建,包含肺腺癌的分子亚型和风险评估模型。

Construction of an algorithm based on oncosis-related LncRNAs comprising the molecular subtypes and a risk assessment model in lung adenocarcinoma.

机构信息

Department of Cardiothoracic Surgery, The Affiliated Lihuili Hospital, Ningbo University, Ningbo, China.

Department of Urology, Ningbo City First Hospital, Ningbo, China.

出版信息

J Clin Lab Anal. 2022 Jun;36(6):e24461. doi: 10.1002/jcla.24461. Epub 2022 Apr 27.

Abstract

BACKGROUND

As an important non-apoptotic cell death method, oncosis has been reported to be closely associated with tumors in recent years. However, few research reported the relationship between oncosis and lung cancer.

METHODS

In this study, we established an oncosis-based algorithm comprised of cluster grouping and a risk assessment model to predict the survival outcomes and related tumor immunity of patients with lung adenocarcinomas (LUAD). We selected 11 oncosis-related lncRNAs associated with the prognosis (CARD8-AS1, LINC00941, LINC01137, LINC01116, AC010980.2, LINC00324, AL365203.2, AL606489.1, AC004687.1, HLA-DQB1-AS1, and AL590226.1) to divide the LUAD patients into different clusters and different risk groups. Compared with patients in clsuter1, patients in cluster2 had a survival advantage and had a relatively more active tumor immunity. Subsequently, we constructed a risk assessment model to distinguish between patients into different risk groups, in which low-risk patients tend to have a better prognosis. GO enrichment analysis revealed that the risk assessment model was closely related to immune activities. In addition, low-risk patients tended to have a higher content of immune cells and stromal cells in tumor microenvironment, higher expression of PD-1, CTLA-4, HAVCR2, and were more sensitive to immune checkpoint inhibitors (ICIs), including PD-1/CTLA-4 inhibitors. The risk score had a significantly positive correlation with tumor mutation burden (TMB). The survival curve of the novel oncosis-based algorithm suggested that low-risk patients in cluster2 have the most obvious survival advantage.

CONCLUSION

The novel oncosis-based algorithm investigated the prognosis and the related tumor immunity of patients with LUAD, which could provide theoretical support for customized individual treatment for LUAD patients.

摘要

背景

作为一种重要的非凋亡性细胞死亡方式,近年来有报道称胀亡与肿瘤密切相关。然而,关于胀亡与肺癌的关系的研究较少。

方法

在这项研究中,我们建立了一个基于胀亡的算法,包括聚类分组和风险评估模型,以预测肺腺癌(LUAD)患者的生存结局和相关肿瘤免疫。我们选择了 11 个与预后相关的胀亡相关 lncRNA(CARD8-AS1、LINC00941、LINC01137、LINC01116、AC010980.2、LINC00324、AL365203.2、AL606489.1、AC004687.1、HLA-DQB1-AS1 和 AL590226.1)将 LUAD 患者分为不同的聚类和不同的风险组。与 cluster1 中的患者相比,cluster2 中的患者具有生存优势,且肿瘤免疫更为活跃。随后,我们构建了一个风险评估模型,以区分不同风险组的患者,其中低风险患者的预后较好。GO 富集分析表明,风险评估模型与免疫活性密切相关。此外,低风险患者的肿瘤微环境中免疫细胞和基质细胞含量较高,PD-1、CTLA-4、HAVCR2 表达较高,对免疫检查点抑制剂(ICIs),包括 PD-1/CTLA-4 抑制剂更为敏感。风险评分与肿瘤突变负荷(TMB)呈显著正相关。基于新型胀亡的算法的生存曲线表明,cluster2 中的低风险患者具有最明显的生存优势。

结论

该新型基于胀亡的算法研究了 LUAD 患者的预后和相关肿瘤免疫,可为 LUAD 患者的个体化治疗提供理论支持。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/32aa/9169186/5b603316b7df/JCLA-36-e24461-g007.jpg

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