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宫颈腺癌预后关键基因的机器学习建模与分析:增强免疫监视的多靶点治疗

Machine learning modeling and analysis of prognostic hub genes in cervical adenocarcinoma: a multi target therapy for enhancement in immunosurveillance.

作者信息

Abbasi Madiha Jabeen, Abbasi Rashid, Wu ShuPeng, Heyat Md Belal Bin, Xianfeng Ding, Jia Huijie, Zheng Aiwen

机构信息

School of Life Science and Medicine, Zhejiang Sci-Tech University, Hangzhou, 310018, China.

College of Computer Science and Artificial Intelligent, Wenzhou University, Wenzhou, China.

出版信息

Discov Oncol. 2025 Jul 13;16(1):1326. doi: 10.1007/s12672-025-02834-3.

Abstract

Endocervical adenocarcinoma (ECA) the fatal and intrusive subtype of cervical carcinoma is on rise from the last decade. Its improper detection leads to worst clinical outcomes that urges the discovery of novel biomarkers. Therefore, we proposed insilico and invitro based approches to identify key genes that could be used as potential targeted therapies. RNA-seq and gene expression data was operated via R-programming that identified 11,592 differential expressed genes which are mainly enriched in metabolic pathways, chemical carcinogenesis-receptor activation, amoebias, MAPK and PI3K-AKT signaling pathway. Clustering modules and hub genes were retrieved to design network of immune cells with varying expression using multiple statistical algorithms. The Drugs targeting hub genes were determined from Drug gene interaction database which was further categorized for docking and dynamics based simulations. Results indicate high binding affinity of Imatinib compound into active pockets of BIRC5 which is confirmed by cell viability lab experiment. Current study demonstrates novel biomarkers and therapeutic drugs for in depth understanding of endocervical carcinogensis.

摘要

宫颈管腺癌(ECA)是宫颈癌致命且具有侵袭性的亚型,在过去十年中呈上升趋势。其检测不当会导致最差的临床结果,这促使人们发现新的生物标志物。因此,我们提出了基于计算机模拟和体外实验的方法来识别可作为潜在靶向治疗的关键基因。通过R编程对RNA测序和基因表达数据进行操作,识别出11592个差异表达基因,这些基因主要富集于代谢途径、化学致癌作用-受体激活、阿米巴病、丝裂原活化蛋白激酶(MAPK)和磷脂酰肌醇-3-激酶-蛋白激酶B(PI3K-AKT)信号通路。使用多种统计算法检索聚类模块和枢纽基因,以设计具有不同表达的免疫细胞网络。从药物-基因相互作用数据库中确定靶向枢纽基因的药物,并进一步将其分类用于基于对接和动力学的模拟。结果表明伊马替尼化合物与凋亡抑制蛋白5(BIRC5)的活性口袋具有高结合亲和力,这在细胞活力实验室实验中得到了证实。当前研究展示了用于深入了解宫颈管癌发生的新生物标志物和治疗药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/038b/12256379/c2a683a8f120/12672_2025_2834_Fig5_HTML.jpg

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