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一种用于预测肺腺癌预后和治疗反应的新型乳酸化相关基因特征。

A novel lactylation-related gene signature to predict prognosis and treatment response in lung adenocarcinoma.

作者信息

Zhang Hongyi, Liu Yihao, Li Xuanguang, Ding Chen, Xia Chunqiu, Huang Hua, Liu Hongyu, Chen Jun

机构信息

Department of Lung Cancer Surgery, Tianjin Medical University General Hospital, Tianjin, China.

Department of Thoracic Surgery, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.

出版信息

Front Oncol. 2025 Mar 14;15:1549724. doi: 10.3389/fonc.2025.1549724. eCollection 2025.

Abstract

BACKGROUND

Lactylation, a novel post-translational modification, has emerged as a critical regulatory mechanism in various biological processes, including tumor progression. However, its role and associated gene signatures in lung adenocarcinoma (LUAD) remain unclear.

METHODS

RNA sequencing data of LUAD patients were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Unsupervised clustering was used to identify lactylation-related genes. A risk prognostic model was constructed using least absolute shrinkage and selection operator regression analysis and subsequently validated. A nomogram was then employed to optimize the clinical applicability of the risk score. Additionally, various algorithms were used to explore the relationship between the risk score and immune infiltration levels, with model genes analyzed based on single-cell sequencing. The effects of RCCD1 knockdown on LUAD cell proliferation and migration were evaluated through CCK8 and transwell assays.

RESULTS

Higher risk scores were associated with poorer overall survival prognosis. Immune analysis revealed that the risk score may play a role in regulating the tumor microenvironment. Additionally, these risk scores were found to be associated with chemotherapy drug sensitivity. A series of experiments further demonstrated that RCCD1 promotes LUAD cell proliferation and migration .

CONCLUSION

This study highlights the critical role of lactylation-related gene signatures in LUAD and their association with immune cell infiltration, providing insights into potential therapeutic targets and biomarkers for clinical application.

摘要

背景

乳酰化作为一种新型的翻译后修饰,已成为包括肿瘤进展在内的各种生物学过程中的关键调节机制。然而,其在肺腺癌(LUAD)中的作用及相关基因特征仍不清楚。

方法

从癌症基因组图谱(TCGA)和基因表达综合数据库(GEO)获取LUAD患者的RNA测序数据。采用无监督聚类来识别乳酰化相关基因。使用最小绝对收缩和选择算子回归分析构建风险预后模型,随后进行验证。然后采用列线图来优化风险评分的临床适用性。此外,使用各种算法探索风险评分与免疫浸润水平之间的关系,并基于单细胞测序对模型基因进行分析。通过CCK8和Transwell实验评估RCCD1基因敲低对LUAD细胞增殖和迁移的影响。

结果

较高的风险评分与较差的总生存预后相关。免疫分析显示,风险评分可能在调节肿瘤微环境中发挥作用。此外,发现这些风险评分与化疗药物敏感性相关。一系列实验进一步证明,RCCD1促进LUAD细胞增殖和迁移。

结论

本研究突出了乳酰化相关基因特征在LUAD中的关键作用及其与免疫细胞浸润的关联,为临床应用中的潜在治疗靶点和生物标志物提供了见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1cc2/11949803/92bb48730257/fonc-15-1549724-g001.jpg

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