| 引用本文: | 杨佳启,李昊,姜楠,闫洪锋,孙培鸣,张涛,周金莲,孙宏伟,崔彦.基于生物信息学分析寻找胰腺癌新的诊断和治疗靶点[J].生物信息学,2022,20(2):100-112. |
| YANG Jiaqi,LI Hao,JIANG Nan,YAN Hongfeng,SUN Peiming,ZHANG Tao,ZHOU Jinlian,SUN Hongwei,CUI Yan.Potential diagnostic and therapecrtic taigets for pancreatic cancer based on bioinformatics[J].Chinese Journal of Bioinformatics,2022,20(2):100-112. |
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| 基于生物信息学分析寻找胰腺癌新的诊断和治疗靶点 |
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杨佳启1,2,李昊2,姜楠3,闫洪锋2,孙培鸣2,张涛2,周金莲4,孙宏伟2,崔彦1,2
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(1.北京大学解放军306医院教学医院 普通外科,北京 100101;2.战略支援部队特色医学中心 普通外科,北京 100101;3.清华长庚医院 肝胆胰治疗中心,北京 102218;4.战略支援部队特色医学中心 病理科,北京 100101)
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| 摘要: |
| 胰腺癌作为一种消化系统高度恶性的肿瘤性疾病,其发生和进展的分子机制仍不确定。为寻找与胰腺癌发生和进展有关的新的有效治疗靶点和潜在的生物标志物。利用GEO数据库中的GEO2R在线工具对胰腺癌组织和正常对照组织的基因表达进行差异分析并对差异表达基因(DEGs)进行GO功能和KEGG通路富集分析。然后通过GEPIA数据库中胰腺癌的转录数据对候选基因的表达进行验证。Kaplan-Meier法分析各候选基因的预后价值。利用starBase数据库中的7个预测程序对候选基因上游潜在的miRNAs进行预测。此外,还使用miRNet和starBase预测了hsa-miR-20b-5p的上游lncRNAs并利用lncATLAS数据库对潜在的lncRNAs进行亚细胞定位。在本研究中,我们发现胰腺癌组织中LAMA3基因的转录水平明显高于健康对照组织。同时,LAMA3的过表达与胰腺癌患者较差的临床预后相关。随后,预测了21个可能靶向LAMA3的潜在上游miRNAs。在预测到的miRNA-mRNA调控轴中,has-miR-20b-5p-LAMA3轴在胰腺癌的发生和进展中具有较高的潜力。进一步研究发现,FGD5-AS1潜在的抑制has-miR-20b-5p-LAMA3调控轴的作用可能能够在胰腺癌中作为诊断和治疗的有效靶点。FGD5-AS1-has-miR-20b-5p-LAMA3调控网络在胰腺癌发生和发展中的具有关键作用,可作为胰腺癌临床诊断和治疗的潜在靶点和生物标志物。 |
| 关键词: 胰腺癌 ceRNAs miRNA lncRNA LAMA3 生物标志物 |
| DOI：10.12113/202104021 |
| 分类号:R735.9 |
| 文献标识码:A |
| 基金项目:国家重大基础科学研究计划项目(No.2013CB945501); 2019年度战略支援部队特色医学中心博士毕业生科研启动基金(No.19ZX08). |
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| Potential diagnostic and therapecrtic taigets for pancreatic cancer based on bioinformatics |
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YANG Jiaqi1,2, LI Hao2, JIANG Nan3, YAN Hongfeng2, SUN Peiming2, ZHANG Tao2, ZHOU Jinlian4, SUN Hongwei2, CUI Yan1,2
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(1. Department of General Surgery, The 306th Hospital of PLA-Peking University Teaching Hospital, Beijing 100101, China;2. Department of General Surgery, Strategic Support Force Medical Center, Beijing 100101,China;3. The Center for Hepatopancreatobiliary Diseases, Beijing Tsinghua Changgung Hospital, Beijing 102218, China;4. Department of Pathology, Strategic Support Force Medical Center, Beijing 100101, China)
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| Abstract: |
| Pancreatic cancer is a digestive system malignant tumor, and the molecular mechanism underlying pancreatic cancer remains uncertain. To explore effectual treatment targets and potential bio-markers for pancreatic cancer prognosis, GEO2R in the GEO database was utilized for the analysis of the differentially expressed genes (DEGs) in pancreatic cancer group and control group, and GO function and KEGG pathway enrichment analyses were carried out. Then, the transcriptional data of candidate genes were verified by gene expression profiling interactive analysis (GEPIA). The prognostic value of each candidate gene was tested by Kaplan-Meier analysis. Possible miRNAs were predicted by seven target prediction programs in starBase database. In addition, upstream lncRNAs of hsa-miR-20b-5p were predicted using miRNet and starBase, and the lncATLAS database was used for the intracellular localization of the potential lncRNAs. Results show that the transcriptional level of the LAMA3 gene significantly elevated in pancreatic cancer patients than that in healthy normal controls. In pancreatic cancer patients, the overexpression of LAMA3 associated with a poor clinical prognosis. Subsequently, 21 potential upstream miRNAs that may target LAMA3 were predicted. For all miRNA-mRNA pairs in the prediction, the has-miR-20b-5p-LAMA3 axis presented the highest potential in the initiation and development of pancreatic cancer. Moreover, FGD5-AS1 was identified to potentially inhibit the has-miR-20b-5p-LAMA3 pathway in pancreatic cancer,which may be used as potential treatment targets. The regulatory roles of the FGD5-AS1-has-miR-20b-5p-LAMA3 network in the initiation and development of pancreatic cancer were analysed, providing potential effectual treatment targets and biomarkers for clinical prognosis. |
| Key words: Pancreatic cancer ceRNA miRNA lncRNA LAMA3 Bio-markers |
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