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胰腺癌关键生物标志物的生物信息学与实验分析

Bioinformatic and experimental analyses of key biomarkers in pancreatic cancer.

作者信息

Ren Tianyu, Xue Xiaofei, Wang Xiaogang, Zhou Xingtong, Dang Shengchun

机构信息

Department of General Surgery, The Affiliated Hospital, Jiangsu University, Zhenjiang, Jiangsu 212001, P.R. China.

Department of General Surgery, Pucheng Hospital, Weinan, Shaanxi 715500, P.R. China.

出版信息

Exp Ther Med. 2021 Dec;22(6):1359. doi: 10.3892/etm.2021.10794. Epub 2021 Sep 24.

DOI:10.3892/etm.2021.10794
PMID:34659505
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8515505/
Abstract

The present study aimed to screen the key genes in pancreatic cancer and to explore the pathogenesis of pancreatic cancer. A total of three expression profiling datasets (GSE28735, GSE16515 and GSE15471) associated with pancreatic cancer were retrieved from the public gene chip database. The differentially expressed genes (DEGs) were screened by GEO2R and subjected to Gene Ontology (GO) and signaling pathway enrichment analysis. Furthermore, a protein interaction network was constructed. The GEPIA online database was used to screen for genes that affect the prognosis of pancreatic cancer. Finally, cell functional experiments were performed on the selected key genes. A total of 72 DEGs were identified, including 52 upregulated and 20 downregulated genes. Enrichment analysis revealed roles of the DEGs in endodermal cell differentiation, cell adhesion, extracellular matrix-receptor interaction and PI3K-Akt signaling pathway. In total, 10 key nodal genes were identified, including integrin subunit α 2 (ITGA2), ITGB6 and collagen α 1 chain 1. Through survival analysis, two genes with an impact on the prognosis of pancreatic cancer were identified, namely ITGA2 and ITGB6. Silencing of ITGB6 in a pancreatic cancer cell line significantly suppressed cell proliferation and induced cell cycle arrest at G2/M phase. The identified key genes and signaling pathways may help to deepen the understanding of the molecular mechanisms involved in pancreatic cancer and provide a theoretical basis to develop novel therapies.

摘要

本研究旨在筛选胰腺癌中的关键基因,并探讨胰腺癌的发病机制。从公共基因芯片数据库中检索了总共三个与胰腺癌相关的表达谱数据集(GSE28735、GSE16515和GSE15471)。通过GEO2R筛选差异表达基因(DEG),并进行基因本体论(GO)和信号通路富集分析。此外,构建了蛋白质相互作用网络。使用GEPIA在线数据库筛选影响胰腺癌预后的基因。最后,对选定的关键基因进行细胞功能实验。共鉴定出72个DEG,包括52个上调基因和20个下调基因。富集分析揭示了DEG在内胚层细胞分化、细胞粘附、细胞外基质-受体相互作用和PI3K-Akt信号通路中的作用。总共鉴定出10个关键节点基因,包括整合素亚基α 2(ITGA2)、ITGB6和胶原蛋白α 1链1。通过生存分析,确定了两个影响胰腺癌预后的基因,即ITGA2和ITGB6。在胰腺癌细胞系中沉默ITGB6可显著抑制细胞增殖并诱导细胞周期停滞在G2/M期。所鉴定的关键基因和信号通路可能有助于加深对胰腺癌相关分子机制的理解,并为开发新疗法提供理论依据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0817/8515505/b41bb243c841/etm-22-06-10794-g05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0817/8515505/7077c786b263/etm-22-06-10794-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0817/8515505/267d79a22d09/etm-22-06-10794-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0817/8515505/0b0e0f3b3e3c/etm-22-06-10794-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0817/8515505/7ebede634052/etm-22-06-10794-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0817/8515505/70fdd4989863/etm-22-06-10794-g04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0817/8515505/b41bb243c841/etm-22-06-10794-g05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0817/8515505/7077c786b263/etm-22-06-10794-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0817/8515505/267d79a22d09/etm-22-06-10794-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0817/8515505/0b0e0f3b3e3c/etm-22-06-10794-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0817/8515505/7ebede634052/etm-22-06-10794-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0817/8515505/70fdd4989863/etm-22-06-10794-g04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0817/8515505/b41bb243c841/etm-22-06-10794-g05.jpg

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本文引用的文献

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Identification of a Nine-Gene Signature and Establishment of a Prognostic Nomogram Predicting Overall Survival of Pancreatic Cancer.一种九基因特征的鉴定及预测胰腺癌总生存期的预后列线图的建立
Front Oncol. 2019 Sep 27;9:996. doi: 10.3389/fonc.2019.00996. eCollection 2019.
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Effects of miR-132 on proliferation and apoptosis of pancreatic cancer cells via Hedgehog signaling pathway.miR-132 通过 Hedgehog 信号通路对胰腺癌细胞增殖和凋亡的影响。
Eur Rev Med Pharmacol Sci. 2019 Mar;23(5):1978-1985. doi: 10.26355/eurrev_201903_17236.
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Stromal fibronectin expression in patients with resected pancreatic ductal adenocarcinoma.
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Coexpression of UCA1 and ITGA2 in pancreatic cancer cells target the expression of miR-107 through focal adhesion pathway.在胰腺癌细胞中 UCA1 和 ITGA2 的共表达通过粘着斑通路靶向 miR-107 的表达。
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LncRNA UCA1 impacts cell proliferation, invasion, and migration of pancreatic cancer through regulating miR-96/FOXO3.长链非编码 RNA UCA1 通过调控 miR-96/FOXO3 影响胰腺癌细胞的增殖、侵袭和迁移。
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Palmatine suppresses glutamine-mediated interaction between pancreatic cancer and stellate cells through simultaneous inhibition of survivin and COL1A1.荷叶碱通过同时抑制生存素和 COL1A1 抑制胰腺癌与星状细胞之间的谷氨酰胺介导的相互作用。
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