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循环lncRNA和miRNA相关的ceRNA网络作为非霍奇金淋巴瘤潜在的预后生物标志物:生物信息学分析及初步研究

Circulating lncRNA- and miRNA-Associated ceRNA Network as a Potential Prognostic Biomarker for Non-Hodgkin Lymphoma: A Bioinformatics Analysis and a Pilot Study.

作者信息

Fernandes Mara, Marques Herlander, Teixeira Ana Luísa, Medeiros Rui

机构信息

Molecular Oncology and Viral Pathology Group, Research Center of IPO Porto (CI-IPOP)/RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto)/Porto Comprehensive Cancer Center (Porto.CCC), 4200-072 Porto, Portugal.

Research Department of the Portuguese League against Cancer Regional Nucleus of the North (LPCC-NRN), 4200-177 Porto, Portugal.

出版信息

Biomedicines. 2022 Jun 4;10(6):1322. doi: 10.3390/biomedicines10061322.

Abstract

Non-Hodgkin lymphoma (NHL) is characterized by a great variability in patient outcomes, resulting in the critical need for identifying new molecular prognostic biomarkers. This study aimed to identify novel circulating prognostic biomarkers based on an miRNA/lncRNA-associated ceRNA network for NHL. Using bioinformatic analysis, we identified the miRNA-lncRNA pairs, and using RT-qPCR, we analyzed their plasma levels in a cohort of 113 NHL patients to assess their prognostic value. Bioinformatic analysis identified SNHG16 and SNHG6 as hsa-miR-20a-5p and hsa-miR-181a-5p sponges, respectively. Plasma levels of hsa-miR-20a-5p/SNHG16 and hsa-miR-181a-5p/SNG6 were significantly associated with more aggressive disease and IPI/FLIPI scores. Moreover, we found that patients with risk expression profiles of hsa-miR-20a-5p/SNHG16 and hsa-miR-181a-5p/SNHG6 presented a higher risk of positive bone marrow involvement. Moreover, hsa-miR-20a-5p/SNHG16 and hsa-miR-181a-5p/SNHG6 pairs' plasma levels were associated with overall survival and progression-free survival of NHL patients, being independent prognostic factors in a multivariate Cox analysis. The prediction models incorporating the ceRNA network expression analysis improved the predictive capacity compared to the model, which only considered the clinicopathological variables. There are still few studies on using the ceRNA network as a potential prognostic biomarker, particularly in NHL, which may permit the implementation of a more personalized management of these patients.

摘要

非霍奇金淋巴瘤(NHL)的特点是患者预后差异很大,因此迫切需要识别新的分子预后生物标志物。本研究旨在基于miRNA/lncRNA相关的ceRNA网络识别NHL新的循环预后生物标志物。通过生物信息学分析,我们鉴定了miRNA-lncRNA对,并使用RT-qPCR分析了113例NHL患者队列中的血浆水平,以评估其预后价值。生物信息学分析分别将SNHG16和SNHG6鉴定为hsa-miR-20a-5p和hsa-miR-181a-5p的海绵。hsa-miR-20a-5p/SNHG16和hsa-miR-181a-5p/SNG6的血浆水平与更具侵袭性的疾病以及IPI/FLIPI评分显著相关。此外,我们发现具有hsa-miR-20a-5p/SNHG16和hsa-miR-181a-5p/SNHG6风险表达谱型的患者骨髓受累阳性风险更高。此外,hsa-miR-20a-5p/SNHG16和hsa-miR-181a-5p/SNHG6对的血浆水平与NHL患者的总生存期和无进展生存期相关,在多变量Cox分析中是独立的预后因素。与仅考虑临床病理变量的模型相比,纳入ceRNA网络表达分析的预测模型提高了预测能力。关于将ceRNA网络用作潜在预后生物标志物的研究仍然很少,特别是在NHL中,这可能允许对这些患者实施更个性化的管理。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/66eb/9219780/517938653d1c/biomedicines-10-01322-g001a.jpg

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