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通过综合生物信息学分析鉴定参与肺腺癌进展和奥希替尼耐药的SUMO化修饰因子。

Identification of SUMOylation modifiers involved in lung adenocarcinoma progression and Osimertinib resistance by integrated bioinformatics analysis.

作者信息

Yang Xiaoping, Liu Yongji, Jiang Wen, Liu Xiaochun, Zhang Xiaonan, Liu Huiying, Xing Daijun, Wang Keer, Zheng Xin, Jiang Wenqing

机构信息

College of First Clinical Medical, Shandong University of Traditional Chinese Medicine, Jinan, China.

Qingdao Traditional Chinese Medicine Hospital, Qingdao Hiser Hospital Affiliated of Qingdao University, Qingdao, 266033, China.

出版信息

Sci Rep. 2025 Aug 24;15(1):31130. doi: 10.1038/s41598-025-16615-z.

Abstract

This study investigates the mechanisms of Osimertinib resistance in lung adenocarcinoma (LUAD) by identifying prognostic genes associated with SUMOylation. We performed differential expression analysis to identify differentially expressed genes (DEGs) in LUAD samples, Osimertinib-tolerant cell samples and SUMOylation-related genes (SRGs). Utilizing Cox regression and LASSO regression, we developed a prognostic model that highlighted five key prognostic genes-BIRC5, AURKA, BLM, NR3C2, and NDC1. These genes were significantly associated with LUAD progression, revealing their predominant expression in epithelial cells, which play a vital role in tumor development. Furthermore, we explored the biological functions and signaling pathways linked to these prognostic genes, discovering that their expression levels and corresponding risk scores could serve as indicators of CD4 T cell and memory B cell activation. The enriched signaling pathways in LUAD were regulated by ubiquitin-related small modifiers, highlighting the complex interplay between SUMOylation and tumor biology. Our findings suggest the important role of SUMOylation-regulated genes in LUAD progression and Osimertinib resistance, suggesting their potential as valuable biomarkers for prognosis and therapeutic targets to enhance treatment strategies for patients with EGFR-mutant lung adenocarcinoma.

摘要

本研究通过鉴定与SUMO化相关的预后基因,探讨肺腺癌(LUAD)中奥希替尼耐药的机制。我们进行了差异表达分析,以鉴定LUAD样本、奥希替尼耐受细胞样本和SUMO化相关基因(SRG)中的差异表达基因(DEG)。利用Cox回归和LASSO回归,我们构建了一个预后模型,该模型突出了五个关键预后基因——BIRC5、AURKA、BLM、NR3C2和NDC1。这些基因与LUAD进展显著相关,揭示了它们在上皮细胞中的主要表达,上皮细胞在肿瘤发展中起着至关重要的作用。此外,我们探索了与这些预后基因相关的生物学功能和信号通路,发现它们的表达水平和相应的风险评分可作为CD4 T细胞和记忆B细胞活化的指标。LUAD中富集的信号通路受泛素相关小修饰因子调控,突出了SUMO化与肿瘤生物学之间复杂的相互作用。我们的研究结果表明SUMO化调控基因在LUAD进展和奥希替尼耐药中具有重要作用,提示它们作为预后有价值的生物标志物和治疗靶点的潜力,以加强对EGFR突变肺腺癌患者的治疗策略。

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