Hu Bowen, Chen Xin, Zou Dan, Du Xiaoyue, Feng Sitong, Shen Yiwen, Sha Xiaofeng, Jiang Feng, Zhou Guoren, Lin Fan, Käsmann Lukas, Shen Bo
Department of Oncology, The Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing, China.
Department of Oncology, Huai'an People's Hospital of Hongze District, Huai'an, China.
Transl Lung Cancer Res. 2025 Mar 31;14(3):940-962. doi: 10.21037/tlcr-2025-204. Epub 2025 Mar 27.
Lung adenocarcinoma (LUAD) is one of the most common tumors in terms of incidence and mortality worldwide. Posttranslational modifications, including crotonylation, play a crucial role in various biological processes and diseases. However, the role of crotonylation in LUAD remains unclear. Our research focuses on identifying key genes in LUAD that are linked to crotonylation and prognosis. We also aim to clarify their role in the LUAD microenvironment to advance clinical translation of related targets.
We used RNA-sequencing data from The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) database to identify differentially expressed genes (DEGs) related to crotonylation in LUAD. Weighted correlation network analysis (WGCNA) was applied to construct gene networks, and hub genes were identified using protein-protein interaction (PPI) analysis. The prognostic value of hub genes was assessed using Kaplan-Meier plots, and the correlation with immune infiltration was analyzed via Tumor Immune Estimation Resource (TIMER) and other algorithms. We then verified these genes through clinical samples and confirmed the role of in LUAD.
We identified , , , and as potential crotonylation-related biomarkers for LUAD. These genes were found to be overexpressed in LUAD and were associated with poor prognosis. They also showed significant correlations with immune cell infiltration and immune-inflammatory pathways. Functional experiments confirmed that knockdown inhibited cell proliferation and migration, induced apoptosis, and enhanced the efficacy of immunotherapy in LUAD.
Our study suggests that crotonylation-related genes, particularly , may serve as novel therapeutic targets and diagnostic markers for LUAD.
肺腺癌(LUAD)是全球发病率和死亡率最高的常见肿瘤之一。包括巴豆酰化在内的翻译后修饰在各种生物过程和疾病中起着关键作用。然而,巴豆酰化在肺腺癌中的作用仍不清楚。我们的研究重点是确定肺腺癌中与巴豆酰化和预后相关的关键基因。我们还旨在阐明它们在肺腺癌微环境中的作用,以推动相关靶点的临床转化。
我们使用来自癌症基因组图谱(TCGA)和基因型-组织表达(GTEx)数据库的RNA测序数据,以识别肺腺癌中与巴豆酰化相关的差异表达基因(DEG)。应用加权基因共表达网络分析(WGCNA)构建基因网络,并使用蛋白质-蛋白质相互作用(PPI)分析确定枢纽基因。使用Kaplan-Meier图评估枢纽基因的预后价值,并通过肿瘤免疫估计资源(TIMER)和其他算法分析与免疫浸润的相关性。然后,我们通过临床样本验证了这些基因,并证实了它们在肺腺癌中的作用。
我们确定了[具体基因名称1]、[具体基因名称2]、[具体基因名称3]和[具体基因名称4]作为肺腺癌潜在的巴豆酰化相关生物标志物。这些基因在肺腺癌中过度表达,并与不良预后相关。它们还与免疫细胞浸润和免疫炎症途径显示出显著相关性。功能实验证实,[具体基因名称1]敲低可抑制细胞增殖和迁移,诱导细胞凋亡,并增强肺腺癌免疫治疗的疗效。
我们的研究表明,巴豆酰化相关基因,特别是[具体基因名称1],可能作为肺腺癌的新型治疗靶点和诊断标志物。