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胰胆管合流异常患儿lncRNAs的表达:功能分析及潜在生物标志物

Expression of lncRNAs in children with pancreaticobiliary maljunction: functional analysis and potential biomarkers.

作者信息

Zhao Lian, Shi San-Li, Guo Wan-Liang

机构信息

Children's Hospital of Soochow University, China.

8 Hospital of Xi'an, China.

出版信息

Arch Med Sci. 2022 Jan 6;20(2):528-538. doi: 10.5114/aoms/145482. eCollection 2024.

Abstract

INTRODUCTION

Pancreaticobiliary maljunction (PBM) leads to higher rates of complications, including cholangitis, pancreatitis, and malignancies. The aim of the present study was to investigate the expression profile of long non-coding RNAs (lncRNAs) and their potential role as biomarkers in children with pancreaticobiliary maljunction.

MATERIAL AND METHODS

The differential expression of lncRNAs and messenger RNA (mRNAs) from pediatric patients with pancreaticobiliary maljunction and control subjects was analyzed using a commercial microarray and later validated with qRT-PCR. The potential biological functions of differentially expressed genes were explored based on Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment. The ability of potential lncRNA biomarkers to predict pancreaticobiliary maljunction was assessed based on the area under the receiver operating characteristic curve (AUC).

RESULTS

There were 2915 mRNAs and 173 lncRNAs upregulated, and 2121 mRNAs and 316 lncRNAs downregulated in PBM cases compared to controls. The enriched Gene Ontology categories associated with differentially expressed mRNAs were extracellular matrix, extracellular region, and kinetochore. The most enriched Kyoto Encyclopedia pathway was protein digestion and absorption, which was associated with cancer and PI3K-Akt signaling. Analysis of - and -target genes predicted that a single lncRNA was able to regulate several mRNAs. The qRT-PCR results for , , and were consistent with the microarray results, and the difference was statistically significant for , , and ( < 0.05). AUC was significant only for (0.837, < 0.001).

CONCLUSIONS

Our results implicate lncRNAs in common bile duct pathogenesis in PBM, and they identify as a potential biomarker for the disease.

摘要

引言

胰胆管合流异常(PBM)会导致更高的并发症发生率,包括胆管炎、胰腺炎和恶性肿瘤。本研究的目的是调查长链非编码RNA(lncRNA)的表达谱及其作为胰胆管合流异常儿童生物标志物的潜在作用。

材料与方法

使用商业微阵列分析胰胆管合流异常儿科患者和对照受试者lncRNA和信使核糖核酸(mRNA)的差异表达,随后用定量逆转录聚合酶链反应(qRT-PCR)进行验证。基于基因本体论和京都基因与基因组百科全书通路富集,探索差异表达基因的潜在生物学功能。基于受试者工作特征曲线(AUC)下面积评估潜在lncRNA生物标志物预测胰胆管合流异常的能力。

结果

与对照组相比,PBM病例中有2915个mRNA和173个lncRNA上调,2121个mRNA和316个lncRNA下调。与差异表达mRNA相关的富集基因本体论类别是细胞外基质、细胞外区域和动粒。最富集的京都基因与基因组百科全书通路是蛋白质消化和吸收,其与癌症和PI3K-Akt信号传导相关。对-和-靶基因的分析预测单个lncRNA能够调节多个mRNA。、和的qRT-PCR结果与微阵列结果一致,且、和的差异具有统计学意义(<0.05)。仅对具有显著的AUC(0.837,<0.001)。

结论

我们的结果表明lncRNA参与PBM中胆总管的发病机制,并将鉴定为该疾病的潜在生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f9a2/11094826/f58206ff1789/AMS-20-2-145482-g001.jpg

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