基于差异共表达网络的lncRNA相关宫颈癌预后模型构建及关键基因EGFR-AS1功能研究

IF 3.3 3区 医学 Q2 ONCOLOGY
Journal of Cancer Pub Date : 2025-03-31 eCollection Date: 2025-01-01 DOI:10.7150/jca.108429
Kailong Du, Qian Chen, Hui Fan, Yunlong Lei, Jian Zhang
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引用次数: 0

摘要

宫颈癌是一种常见的妇科恶性肿瘤,平均发病年龄逐渐降低。因此,迫切需要一种有效的预测模型来提高宫颈癌患者的个性化治疗。长链非编码rna (Long non-coding rna, lncRNAs)在恶性肿瘤的发生、发展和预后中起着至关重要的作用。本研究利用宫颈癌多组学数据和单细胞测序数据进行分析,采用集成学习中的随机森林算法和mRNA与lncRNA共表达网络技术建立33-lncRNA-CESC模型。结果表明,该模型具有较强的鉴别能力、准确性和临床实用性。进一步探讨了模型与免疫细胞浸润的关系。富集分析显示该模型与细胞增殖以及表皮生长因子受体(EGFR)信号通路之间存在关联。随后,我们将注意力转向了模型中的EGFR-AS1基因,该基因在共表达网络中被发现,并与患者预后有显著关联。此外,EGFR-AS1被发现与FAM83B特异性相关。单细胞数据分析证实FAM83B主要通过EGFR信号通路参与宫颈癌晚期发展。功能实验表明,无论是EGFR-AS1还是FAM83B基因敲低,都能抑制宫颈癌细胞的增殖和迁移能力,并抑制磷酸化的ERK和AKT水平。此外,EGFR-AS1与FAM83B表达之间存在相互调节作用。总之,本研究确定EGFR- as1在我们的33-lncRNA-CESC模型中是一个关键因子,并可能与FAM83B相互作用,调节EGFR通路,显著影响宫颈癌的发展。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Construction of a Prognostic Model for Cervical Cancer Related to lncRNA Based on Differential Co-expression Network and Functional Study of Key Gene EGFR-AS1.

Cervical cancer is a common gynecological malignancy, and the average age of onset is decreasing gradually. Therefore, an effective predictive model is urgently needed to improve the personalized treatment of cervical cancer patients. Long non-coding RNAs (lncRNAs) play crucial roles in the occurrence, development, and prognosis of malignant tumors. In this study, we used cervical cancer multi-omics data and single-cell sequencing data for analysis, and established a 33-lncRNA-CESC model by using the random forest algorithm in ensemble learning and mRNA and lncRNA co-expression network technology. The results demonstrated that the model exhibited strong discriminative ability, accuracy, and clinical utility. Furthermore, we investigated the relationship between the model and immune cell infiltration. Enrichment analysis revealed associations between the model and cellular proliferation as well as epidermal growth factor receptor (EGFR) signaling pathways. Subsequently, attention was directed toward the gene EGFR-AS1 in the model, which was identified within the co-expression network and exhibited a significant association with patient prognosis. Additionally, EGFR-AS1 was found to be specifically associated with FAM83B. Analysis of single-cell data confirmed that FAM83B plays a role in the late stage of cervical cancer development mainly through the EGFR signaling pathway. Functional experiments showed that knockdown of either EGFR-AS1 or FAM83B inhibited cervical cancer cell proliferation and migration capabilities, and the phosphorylated ERK and AKT levels. In addition, there was a mutual regulatory effect between EGFR-AS1 and FAM83B expression. In conclusion, this study identifies that EGFR-AS1 served as a key factor in our 33-lncRNA-CESC model and potentially interacted with FAM83B to regulate the EGFR pathway which significantly impacting cervical cancer development.

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来源期刊
Journal of Cancer
Journal of Cancer ONCOLOGY-
CiteScore
8.10
自引率
2.60%
发文量
333
审稿时长
12 weeks
期刊介绍: Journal of Cancer is an open access, peer-reviewed journal with broad scope covering all areas of cancer research, especially novel concepts, new methods, new regimens, new therapeutic agents, and alternative approaches for early detection and intervention of cancer. The Journal is supported by an international editorial board consisting of a distinguished team of cancer researchers. Journal of Cancer aims at rapid publication of high quality results in cancer research while maintaining rigorous peer-review process.
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