Developing and validating a survival prediction model based on blood exosomal ceRNA network in patients with PAAD

BMC Medical Genomics

Research

Qingqing Wang¹  Lijun Xu¹  Dan Zhang¹  Shanshan Wang¹  Chongyu Wang²  Kangle Zhu²  Huixia Zhu³ 

[1] Department of General Surgery, Affiliated Hospital of Nantong University, Medical School of Nantong University, 226001, Nantong City, Jiangsu Province, China;Department of Medicine, Xinglin college, Nantong University, Nantong City, Jiangsu Province, China;Medical School of Nantong University, 226001, Nantong City, China;

关键词: Pancreatic adenocarcinoma;    Exosomes;    Competing endogenous RNA;    Regulatory networks;    Enrichment analysis;    Survival prediction model;   

DOI  :  10.1186/s12920-022-01409-3

 received in 2022-07-08, accepted in 2022-12-06,  发布年份 2022

来源: Springer

【 摘 要 】

BackgroundAmong the most lethal cancers, pancreatic adenocarcinoma (PAAD) is an essential component of digestive system malignancies that still lacks effective diagnosis and treatment methods. As exosomes and competing endogenous RNA (ceRNA) regulatory networks in tumors go deeper, we expect to construct a ceRNA regulatory network derived from blood exosomes of PAAD patients by bioinformatics methods and develop a survival prediction model based on it.MethodsBlood exosome sequencing data of PAAD patients and normal controls were downloaded from the exoRbase database, and the expression profiles of exosomal mRNA, lncRNA, and circRNA were differentially analyzed by R. The related mRNA, circRNA, lncRNA, and their corresponding miRNA prediction data were imported into Cytoscape software to visualize the ceRNA network. Then, we conducted GO and KEGG enrichment analysis of mRNA in the ceRNA network. Genes that express differently in pancreatic cancer tissues compared with normal tissues and associate with survival (P < 0.05) were determined as Hub genes by GEPIA. We identified optimal prognosis-related differentially expressed mRNAs (DEmRNAs) and generated a risk score model by performing univariate and multivariate Cox regression analyses.Results205 DEmRNAs, 118 differentially expressed lncRNAs (DElncRNAs), and 98 differentially expressed circRNAs (DEcircRNAs) were screened out. We constructed the ceRNA network, and a total of 26 mRNA nodes, 7 lncRNA nodes, 6 circRNA nodes, and 16 miRNA nodes were identified. KEGG enrichment analysis showed that the DEmRNAs in the regulatory network were mainly enriched in Human papillomavirus infection, PI3K-Akt signaling pathway, Osteoclast differentiation, and ECM-receptor interaction. Next, six hub genes (S100A14, KRT8, KRT19, MAL2, MYO5B, PSCA) were determined through GEPIA. They all showed significantly increased expression in cancer tissues compared with control groups, and their high expression pointed to adverse survival. Two optimal prognostic-related DEmRNAs, MYO5B (HR = 1.41, P < 0.05) and PSCA (HR = 1.10, P < 0.05) were included to construct the survival prediction model.ConclusionIn this study, we successfully constructed a ceRNA regulatory network in blood exosomes from PAAD patients and developed a two-gene survival prediction model that provided new targets which shall aid in diagnosing and treating PAAD.

【 授权许可】

CC BY   
© The Author(s) 2022

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