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基于二硫键凋亡相关基因的预后模型的鉴定和评估:对肺腺癌免疫微环境和肿瘤生物学的影响。

Identifying and assessing a prognostic model based on disulfidptosis-related genes: implications for immune microenvironment and tumor biology in lung adenocarcinoma.

机构信息

School of Public Health, Suzhou Medical College of Soochow University, Jiangsu, Suzhou, China.

出版信息

Front Immunol. 2024 May 22;15:1371831. doi: 10.3389/fimmu.2024.1371831. eCollection 2024.

Abstract

INTRODUCTION

Lung cancer, with the highest global mortality rate among cancers, presents a grim prognosis, often diagnosed at an advanced stage in nearly 70% of cases. Recent research has unveiled a novel mechanism of cell death termed disulfidptosis, which is facilitated by glucose scarcity and the protein SLC7A11.

METHODS

Utilizing the least absolute shrinkage and selection operator (LASSO) regression analysis combined with Cox regression analysis, we constructed a prognostic model focusing on disulfidptosis-related genes. Nomograms, correlation analyses, and enrichment analyses were employed to assess the significance of this model. Among the genes incorporated into the model, CHRNA5 was selected for further investigation regarding its role in LUAD cells. Biological functions of CHRNA5 were assessed using EdU, transwell, and CCK-8 assays.

RESULTS

The efficacy of the model was validated through internal testing and an external validation set, with further evaluation of its robustness and clinical applicability using a nomogram. Subsequent correlation analyses revealed associations between the risk score and infiltration of various cancer types, as well as oncogene expression. Enrichment analysis also identified associations between the risk score and pivotal biological processes and KEGG pathways. Our findings underscore the significant impact of CHRNA5 on LUAD cell proliferation, migration, and disulfidptosis.

CONCLUSION

This study successfully developed and validated a robust prognostic model centered on disulfidptosis-related genes, providing a foundation for predicting prognosis in LUAD patients.

摘要

简介

肺癌是全球癌症死亡率最高的癌症,预后极差,近 70%的病例在晚期才被诊断出来。最近的研究揭示了一种称为二硫键细胞死亡的新细胞死亡机制,该机制是由葡萄糖缺乏和蛋白质 SLC7A11 介导的。

方法

我们利用最小绝对收缩和选择算子(LASSO)回归分析结合 Cox 回归分析,构建了一个专注于二硫键细胞死亡相关基因的预后模型。我们使用列线图、相关性分析和富集分析来评估该模型的意义。在纳入模型的基因中,我们选择 CHRNA5 进一步研究其在 LUAD 细胞中的作用。使用 EdU、transwell 和 CCK-8 测定评估 CHRNA5 的生物学功能。

结果

通过内部测试和外部验证集验证了该模型的有效性,并进一步使用列线图评估了其稳健性和临床适用性。随后的相关性分析显示,风险评分与各种癌症类型的浸润以及致癌基因表达之间存在关联。富集分析还发现了风险评分与关键生物学过程和 KEGG 途径之间的关联。我们的研究结果强调了 CHRNA5 对 LUAD 细胞增殖、迁移和二硫键细胞死亡的显著影响。

结论

本研究成功开发并验证了一个基于二硫键细胞死亡相关基因的稳健预后模型,为预测 LUAD 患者的预后提供了基础。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b43a/11150594/c73d850d95c6/fimmu-15-1371831-g001.jpg

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