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慢性病毒性肝炎相关肝细胞癌中与炎症相关的长链非编码RNA(lncRNA)

Inflammation-Associated Long Non-Coding RNAs (lncRNAs) in Chronic Viral Hepatitis- Associated Hepatocellular Carcinoma.

作者信息

Pehlivanoglu Burcin, Aysal Anil, Agalar Cihan, Egeli Tufan, Ozbilgin Mucahit, Unek Tarkan, Unek Ilkay Tugba, Oztop Ilhan, Aktas Safiye, Sagol Ozgul

机构信息

Department of Molecular Pathology, Dokuz Eylul University, Graduate School of Health Sciences, IZMIR, TÜRKİYE.

Department of General Surgery, Dokuz Eylul University, Faculty of Medicine, IZMIR, TÜRKİYE.

出版信息

Turk Patoloji Derg. 2025;41(1):1-8. doi: 10.5146/tjpath.2024.13593.

Abstract

OBJECTIVE

This study aimed to identify the expression profile and prognostic significance of inflammation-associated lncRNAs in chronic viral hepatitis (CVH) and CVH-associated hepatocellular carcinoma (CVH-HCC).

MATERIAL AND METHODS

In the first step, lncRNA expression analysis was performed by real-time polymerase chain reaction (RT-PCR) using an array panel of 84 inflammation-associated lncRNAs in 48 formalin-fixed paraffin-embedded (FFPE) tissue samples (12 CVH-HCC, 12 peritumoral cirrhotic parenchyma, 12 nontumoral cirrhotic CVH parenchyma, 12 normal liver samples). In the second step, 7 lncRNAs (DLEU2, HOTAIR, LINC00635, LINC00662, RP11-549J18.1, SNHG16 and XIST) were chosen for RT-PCR assay testing in 72 samples (24 CVH-HCC, 24 peritumoral cirrhotic parenchyma, 24 nontumoral cirrhotic CVH parenchyma samples).

RESULTS

Fifty-six inflammation-associated lncRNAs were significantly up-regulated in the peritumoral cirrhotic parenchyma compared to the normal liver. Expression of 71 lncRNAs was significantly higher in peritumoral cirrhotic parenchyma compared to cirrhotic CVH parenchyma. DLEU2 and SNHG16 were up-regulated both in the tumor and peritumoral cirrhotic parenchyma compared to cirrhotic CVH parenchyma. Expression of LINC00662 was significantly higher in CVH-HCC than in cirrhotic CVH parenchyma. Expression of XIST was also increased in both tumor and peritumoral parenchyma samples, albeit without statistical significance. No significant association was found between lncRNA expressions and survival.

CONCLUSION

Inflammation-associated lncRNAs DLEU2, SNHG16, LINC00662, and XIST are candidate diagnostic biomarkers in CVH-HCC. More evidence is needed to prove their utility as prognostic markers.

摘要

目的

本研究旨在确定炎症相关长链非编码RNA(lncRNA)在慢性病毒性肝炎(CVH)及CVH相关肝细胞癌(CVH-HCC)中的表达谱及预后意义。

材料与方法

第一步,使用包含84种炎症相关lncRNA的阵列,通过实时聚合酶链反应(RT-PCR)对48份福尔马林固定石蜡包埋(FFPE)组织样本(12份CVH-HCC、12份瘤旁肝硬化实质、12份非肿瘤性肝硬化CVH实质、12份正常肝脏样本)进行lncRNA表达分析。第二步,选择7种lncRNA(DLEU2、HOTAIR、LINC00635、LINC00662、RP11-549J18.1、SNHG16和XIST)在72份样本(24份CVH-HCC、24份瘤旁肝硬化实质、24份非肿瘤性肝硬化CVH实质样本)中进行RT-PCR检测。

结果

与正常肝脏相比,瘤旁肝硬化实质中有56种炎症相关lncRNA显著上调。与肝硬化CVH实质相比,瘤旁肝硬化实质中71种lncRNA的表达显著更高。与肝硬化CVH实质相比,DLEU2和SNHG16在肿瘤及瘤旁肝硬化实质中均上调。LINC00662在CVH-HCC中的表达显著高于肝硬化CVH实质。XIST在肿瘤及瘤旁实质样本中的表达也有所增加,尽管无统计学意义。未发现lncRNA表达与生存之间存在显著关联。

结论

炎症相关lncRNA DLEU2、SNHG16、LINC00662和XIST是CVH-HCC的候选诊断生物标志物。需要更多证据来证明它们作为预后标志物的效用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7656/11826398/7d682e57d04d/TurkPatolojiDerg-41-13593-g001.jpg

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