ZNF基因家族在胰腺癌中的诊断意义:一项生物信息学与实验研究

The diagnostic significance of the ZNF gene family in pancreatic cancer: a bioinformatics and experimental study.

作者信息

Zhu Lei, Tu Dong, Li Ruixue, Li Lin, Zhang Wenjie, Jin Wenxiang, Li Tiehan, Zhu Hong

机构信息

Department of Hepatobiliary and Pancreatic Surgery, Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China.

Department of Cardiothoracic Surgery, No. 920 Hospital of the PLA Joint Logistics Support Force, Kunming, China.

出版信息

Front Genet. 2023 Jun 16;14:1089023. doi: 10.3389/fgene.2023.1089023. eCollection 2023.

Abstract

Pancreatic adenocarcinoma (PAAD) is among the most devastating of all cancers with a poor survival rate. Therefore, we established a zinc finger (ZNF) protein-based prognostic prediction model for PAAD patients. The RNA-seq data for PAAD were downloaded from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases. Differentially expressed ZNF protein genes (DE-ZNFs) in PAAD and normal control tissues were screened using the "lemma" package in R. An optimal risk model and an independent prognostic value were established by univariate and multivariate Cox regression analyses. Survival analyses were performed to assess the prognostic ability of the model. We constructed a ZNF family genes-related risk score model that is based on the 10 DE-ZNFs (ZNF185, PRKCI, RTP4, SERTAD2, DEF8, ZMAT1, SP110, U2AF1L4, CXXC1, and RMND5B). The risk score was found to be a significant independent prognostic factor for PAAD patients. Seven significantly differentially expressed immune cells were identified between the high- and low-risk patients. Then, based on the prognostic genes, we constructed a ceRNA regulatory network that includes 5 prognostic genes, 7 miRNAs and 35 lncRNAs. Expression analysis showed ZNF185, PRKCI and RTP4 were significantly upregulated, while ZMAT1 and CXXC1 were significantly downregulated in the PAAD samples in all TCGA - PAAD, GSE28735 and GSE15471 datasets. Moreover, the upregulation of RTP4, SERTAD2, and SP110 were verified by the cell experiments. We established and validated a novel, Zinc finger protein family - related prognostic risk model for patients with PAAD, that has the potential to inform patient management.

摘要

胰腺腺癌(PAAD)是所有癌症中最具毁灭性的癌症之一,生存率很低。因此,我们为PAAD患者建立了一种基于锌指(ZNF)蛋白的预后预测模型。PAAD的RNA测序数据从癌症基因组图谱(TCGA)和基因表达综合数据库(GEO)下载。使用R语言中的“lemma”软件包筛选PAAD和正常对照组织中差异表达的ZNF蛋白基因(DE-ZNFs)。通过单变量和多变量Cox回归分析建立了最佳风险模型和独立预后价值。进行生存分析以评估该模型的预后能力。我们构建了一个基于10个DE-ZNFs(ZNF185、PRKCI、RTP4、SERTAD2、DEF8、ZMAT1、SP110、U2AF1L4、CXXC1和RMND5B)的ZNF家族基因相关风险评分模型。发现风险评分是PAAD患者的一个显著独立预后因素。在高风险和低风险患者之间鉴定出7种显著差异表达的免疫细胞。然后,基于预后基因,我们构建了一个ceRNA调控网络,该网络包括5个预后基因、7个miRNA和35个lncRNA。表达分析表明,在所有TCGA-PAAD、GSE28735和GSE15471数据集中,PAAD样本中ZNF185、PRKCI和RTP4显著上调,而ZMAT1和CXXC1显著下调。此外,细胞实验验证了RTP4、SERTAD2和SP110的上调。我们为PAAD患者建立并验证了一种新型的、与锌指蛋白家族相关的预后风险模型,该模型有可能为患者管理提供参考。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5966/10311482/d64b9ef21750/fgene-14-1089023-g001.jpg

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