System Analysis Based on Pancreatic Cancer Progression Identifies BRINP2 as a Novel Prognostic Biomarker.

IF 1.5 4区 医学 Q4 BIOTECHNOLOGY & APPLIED MICROBIOLOGY
Yixing Kang, Xiangwen Xu, Jikui Liu
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引用次数: 0

Abstract

Pancreatic adenocarcinoma (PAAD) is a malignant tumor of the digestive system, which develops rapidly and has no obvious early symptoms. This study aims to discover the biomarkers associated with PAAD development. We obtained RNA expression of PAAD patient samples and corresponding clinical data from The cancer genome atlas (TCGA), and screened out BMP/RA-inducible neural-specific protein 2 (BRINP2) gene which is highly associated with PAAD severity. Then, gene ontology (GO) enrichment, Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis and single-sample gene set enrichment analysis (ssGSEA) analysis were performed to explore the biological functions of BRINP2. Subsequently, long non-coding RNA (lncRNAs) associated with BRINP2 were screened out via correlation analysis, and Cox regression analysis and least absolute shrinkage selection operator (LASSO) regression analysis were used to construct the risk prediction model. We further validated the expression level of BRINP2 and its associated lncRNAs in BRINP2-associated lncRNAs prognostic model in vitro. We proposed that BRINP2 might be correlated to the tumor immune microenvironment and could also be used as a biomarker for PAAD progression. GO enrichment analysis and KEGG pathway analysis showed that the prognostic model was highly correlated to immune microenvironment-related pathways. Additionally, we established a BRINP2-associated lncRNAs prognostic model consisting of three lncRNAs. We validated the expression trends of BRINP2 and its associated lncRNAs in BRINP2-associated lncRNAs prognostic model in PAAD cells with various severity of metastatic potential using the quantitative real-time PCR (qRT-PCR). Meanwhile, pRRophetic R package was employed to predict potential therapeutic drugs for BRINP2-associated lncRNAs prognostic model of PAAD. The results suggest that BRINP2 can be used as a novel prognostic biomarker for PAAD.

基于胰腺癌进展的系统分析发现 BRINP2 是一种新型预后生物标记物
胰腺腺癌(PAAD)是消化系统的恶性肿瘤,发展迅速,早期无明显症状。本研究旨在发现与 PAAD 发展相关的生物标志物。我们从癌症基因组图谱(TCGA)中获取了PAAD患者样本的RNA表达和相应的临床数据,筛选出与PAAD严重程度高度相关的BMP/RA诱导神经特异性蛋白2(BRINP2)基因。然后,通过基因本体论(GO)富集、京都基因组百科全书(KEGG)通路分析和单样本基因组富集分析(ssGSEA)来探讨BRINP2的生物学功能。随后,通过相关性分析筛选出与BRINP2相关的长非编码RNA(lncRNA),并采用Cox回归分析和最小绝对收缩选择算子(LASSO)回归分析构建风险预测模型。我们进一步在体外验证了BRINP2相关lncRNAs预后模型中BRINP2及其相关lncRNAs的表达水平。我们提出,BRINP2可能与肿瘤免疫微环境相关,也可作为PAAD进展的生物标志物。GO富集分析和KEGG通路分析表明,预后模型与免疫微环境相关通路高度相关。此外,我们还建立了一个由三个lncRNAs组成的BRINP2相关lncRNAs预后模型。我们利用实时定量PCR(qRT-PCR)技术在具有不同程度转移潜能的PAAD细胞中验证了BRINP2及其相关lncRNAs在BRINP2相关lncRNAs预后模型中的表达趋势。同时,利用pRRophetic R软件包预测了PAAD的BRINP2相关lncRNAs预后模型的潜在治疗药物。结果表明,BRINP2可作为一种新型的PAAD预后生物标志物。
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来源期刊
Critical Reviews in Eukaryotic Gene Expression
Critical Reviews in Eukaryotic Gene Expression 生物-生物工程与应用微生物
CiteScore
2.70
自引率
0.00%
发文量
67
审稿时长
1 months
期刊介绍: Critical ReviewsTM in Eukaryotic Gene Expression presents timely concepts and experimental approaches that are contributing to rapid advances in our mechanistic understanding of gene regulation, organization, and structure within the contexts of biological control and the diagnosis/treatment of disease. The journal provides in-depth critical reviews, on well-defined topics of immediate interest, written by recognized specialists in the field. Extensive literature citations provide a comprehensive information resource. Reviews are developed from an historical perspective and suggest directions that can be anticipated. Strengths as well as limitations of methodologies and experimental strategies are considered.
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