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基于TCGA队列鉴定胰腺腺癌的新型候选生物标志物

Identification of novel candidate biomarkers for pancreatic adenocarcinoma based on TCGA cohort.

作者信息

Jie Yang, Peng Wang, Li Yuan-Yuan

机构信息

Department of Pharmacy, Shandong Provincial Hospital, Jinan 250022, Shandong, P.R. China.

Department of Pharmacy, The First Affiliated Hospital of Shandong First Medical University, Jinan 250014, Shandong, P.R. China.

出版信息

Aging (Albany NY). 2021 Feb 11;13(4):5698-5717. doi: 10.18632/aging.202494.

DOI:10.18632/aging.202494
PMID:33591944
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7950294/
Abstract

Pancreatic adenocarcinoma (PAAD) is the most serious solid tumor type throughout the world. The present study aimed to identify novel biomarkers and potential efficacious small drugs in PAAD using integrated bioinformatics analyses. A total of 4777 differentially expressed genes (DEGs) were filtered, 2536 upregulated DEGs and 2241 downregulated DEGs. Weighted gene co-expression network analysis was then used and identified 12 modules, of which, blue module with the most significant enrichment result was selected. KEGG and GO enrichment analyses showed that all DEGs of blue module were enriched in EMT and PI3K/Akt pathway. Three hub genes (, , and ) were determined as key genes with higher expression levels, significant prognostic value and excellent diagnostic efficiency for PAAD. Additionally, some small molecule drugs that possess the potential to treat PAAD were screened out, including thapsigargin (TG). Functional experiments revealed that TG repressed cell viability via inactivating the PI3K/Akt pathway in PAAD cells. Totally, our findings identified three key genes implicated in PAAD and screened out several potential small drugs to treat PAAD.

摘要

胰腺腺癌（PAAD）是全球最严重的实体瘤类型。本研究旨在通过综合生物信息学分析，在PAAD中鉴定新的生物标志物和潜在有效的小分子药物。共筛选出4777个差异表达基因（DEG），其中2536个上调DEG和2241个下调DEG。随后进行加权基因共表达网络分析，鉴定出12个模块，其中选择了富集结果最显著的蓝色模块。KEGG和GO富集分析表明，蓝色模块的所有DEG均富集于上皮-间质转化（EMT）和PI3K/Akt信号通路。确定了三个枢纽基因（、和）作为关键基因，它们在PAAD中具有较高的表达水平、显著的预后价值和良好的诊断效率。此外，筛选出了一些具有治疗PAAD潜力的小分子药物，包括毒胡萝卜素（TG）。功能实验表明，TG通过使PAAD细胞中的PI3K/Akt信号通路失活来抑制细胞活力。总之，我们的研究结果鉴定了PAAD中涉及的三个关键基因，并筛选出了几种治疗PAAD的潜在小分子药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f2e/7950294/39fce2324c1c/aging-13-202494-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f2e/7950294/ecec982e0be4/aging-13-202494-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f2e/7950294/6bb0f8f067aa/aging-13-202494-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f2e/7950294/193b379c71a3/aging-13-202494-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f2e/7950294/a63726a3b059/aging-13-202494-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f2e/7950294/a5b9b15bd9c3/aging-13-202494-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f2e/7950294/39fce2324c1c/aging-13-202494-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f2e/7950294/ecec982e0be4/aging-13-202494-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f2e/7950294/27ecc412adf1/aging-13-202494-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f2e/7950294/6bb0f8f067aa/aging-13-202494-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f2e/7950294/193b379c71a3/aging-13-202494-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f2e/7950294/a63726a3b059/aging-13-202494-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f2e/7950294/a5b9b15bd9c3/aging-13-202494-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f2e/7950294/39fce2324c1c/aging-13-202494-g007.jpg

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