The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, China.
Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, China.
Int Immunopharmacol. 2021 Mar;92:107333. doi: 10.1016/j.intimp.2020.107333. Epub 2021 Jan 21.
An increasing body of evidence has supported that long non-coding RNAs (lncRNAs) can play as essential roles of various physiological process and pathological diseases. We aimed to construct a robust immune-associated lncRNA signature associated with the prognosis for HCC survival prediction.
7 immune-associated lncRNAs presenting significant correlation with survival were screened through stepwise univariate Cox regression and LASSO algorithm, and multivariate Cox regression. Kaplan-Meier analysis, proportional hazards model, and ROC analyses further conducted. Gene set enrichment analysis (GSEA) was applied for functional annotation. We conducted quantitative real-time polymerase chain reaction to determine NRAV expression and preliminarily explored the latent role of NRAV in prognosis of HCC patients.
Finally, 7 immune-related lncRNA signature composed of AC007405.3, AC023157.3, NRAV, CASC19, MSC-AS1, GASAL1, and LINC00942 were validated. This lncRNAs signature can serve as an independent predictive biomolecular factor. This signature was further confirmed in the validation group and the entire cohort. We demonstrated that NRAV was significantly upregulated in HCC cell lines and it may serve as a key regulator in HCC. Our signature was associated to apoptosis and immunologic characteristics. This signature mediated immune cell infiltration (i.e., Dendritic, etc.,) and immune checkpoint blockade (ICB) immunotherapy-related molecules (i.e., CD274, etc.,).
This immune-related lncRNA signature possesses promising prognostic value in HCC and may have the potentiality to predict clinical outcome of ICB immunotherapy.
越来越多的证据表明，长非编码 RNA（lncRNA）可以在各种生理过程和病理疾病中发挥重要作用。我们旨在构建一个稳健的免疫相关 lncRNA 特征，与 HCC 患者的生存预测相关。
通过逐步单因素 Cox 回归和 LASSO 算法以及多因素 Cox 回归筛选出与生存相关的 7 个免疫相关 lncRNA。进行 Kaplan-Meier 分析、比例风险模型和 ROC 分析。进行基因集富集分析（GSEA）进行功能注释。我们进行定量实时聚合酶链反应以确定 NRAV 的表达，并初步探讨 NRAV 在 HCC 患者预后中的潜在作用。
最终，验证了由 AC007405.3、AC023157.3、NRAV、CASC19、MSC-AS1、GASAL1 和 LINC00942 组成的 7 个免疫相关 lncRNA 特征。该 lncRNA 特征可以作为独立的预测生物分子因素。该特征在验证组和整个队列中得到进一步验证。我们表明，NRAV 在 HCC 细胞系中显著上调，它可能作为 HCC 的关键调节剂。我们的特征与细胞凋亡和免疫特征相关。该特征介导免疫细胞浸润（例如，树突状细胞等）和免疫检查点阻断（ICB）免疫治疗相关分子（例如，CD274 等）。
该免疫相关 lncRNA 特征在 HCC 中具有有前途的预后价值，并且可能具有预测 ICB 免疫治疗临床结果的潜力。
