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环状 RNA 与微小 RNA 的 ceRNA 网络作为非霍奇金淋巴瘤的循环预后生物标志物:生物信息学分析及其在 NHL 队列中预后价值的评估。

ceRNA Network of lncRNA/miRNA as Circulating Prognostic Biomarkers in Non-Hodgkin Lymphomas: Bioinformatic Analysis and Assessment of Their Prognostic Value in an NHL Cohort.

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

Int J Mol Sci. 2021 Dec 24;23(1):201. doi: 10.3390/ijms23010201.

Abstract

Research has been focusing on identifying novel biomarkers to better stratify non-Hodgkin lymphoma patients based on prognosis. Studies have demonstrated that lncRNAs act as miRNA sponges, creating ceRNA networks to regulate mRNA expression, and its deregulation is associated with lymphoma development. This study aimed to identify novel circulating prognostic biomarkers based on miRNA/lncRNA-associated ceRNA network for NHL. Herein, bioinformatic analysis was performed to construct ceRNA networks for hsa-miR-150-5p and hsa-miR335-5p. Then, the prognostic value of the miRNA-lncRNA pairs' plasma levels was assessed in a cohort of 113 NHL patients. Bioinformatic analysis identified MALAT1 and NEAT1 as hsa-miR-150-5p and has-miR-335-5p sponges, respectively. Plasma hsa-miR-150-5p/MALAT1 and hsa-miR335-5p/NEAT1 levels were significantly associated with more aggressive and advanced disease. The overall survival and progression-free survival analysis indicated that hsa-miR-150-5p/MALAT1 and hsa-miR335-5p/NEAT1 pairs' plasma levels were remarkably associated with NHL patients' prognosis, being independent prognostic factors in a multivariate Cox analysis. Low levels of hsa-miR-150-5p and hsa-miR-335-5p combined with high levels of the respective lncRNA pair were associated with poor prognosis of NHL patients. Overall, the analysis of ceRNA network expression levels may be a useful prognostic biomarker for NHL patients and could identify patients who could benefit from more intensive treatments.

摘要

研究一直致力于寻找新的生物标志物,以便根据预后更好地对非霍奇金淋巴瘤患者进行分层。研究表明,lncRNAs 作为 miRNA 的海绵,形成 ceRNA 网络来调节 mRNA 的表达,其失调与淋巴瘤的发展有关。本研究旨在基于 miRNA/lncRNA 相关 ceRNA 网络鉴定新的循环预后生物标志物用于 NHL。在此,进行了生物信息学分析,构建了 hsa-miR-150-5p 和 hsa-miR335-5p 的 ceRNA 网络。然后,在 113 例 NHL 患者的队列中评估了 miRNA-lncRNA 对血浆水平的预后价值。生物信息学分析鉴定 MALAT1 和 NEAT1 分别为 hsa-miR-150-5p 和 has-miR-335-5p 的海绵。血浆 hsa-miR-150-5p/MALAT1 和 hsa-miR335-5p/NEAT1 水平与侵袭性更强和更晚期的疾病显著相关。总生存和无进展生存分析表明,hsa-miR-150-5p/MALAT1 和 hsa-miR335-5p/NEAT1 对血浆水平与 NHL 患者的预后显著相关,是多变量 Cox 分析中的独立预后因素。hsa-miR-150-5p 和 hsa-miR-335-5p 水平低结合各自 lncRNA 对水平高与 NHL 患者的预后不良相关。总体而言,ceRNA 网络表达水平的分析可能是 NHL 患者有用的预后生物标志物,并可以识别可能受益于更强化治疗的患者。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/629a/8745130/c31272040133/ijms-23-00201-g001.jpg

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