Department of Obstetrics and Gynecology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, China.
Department of Dermatopathology, Shanghai Skin Disease Hospital, Tongji University School of Medicine, Shanghai 200443, China.
Biomed Res Int. 2021 Jan 5;2021:9798231. doi: 10.1155/2021/9798231. eCollection 2021.
Hepatocellular carcinoma (HCC) ranks fifth among common cancers and is the second most common cause of cancer-related mortality worldwide. This study is aimed at identifying an immune-related long noncoding RNA (lncRNA) signature as a potential biomarker with prognostic value to improve early diagnosis and provide potential therapeutic targets for HCC patients. The subjects of this study were HCC samples with complete transcriptome data and clinical information downloaded from The Cancer Genome Atlas (TCGA) database. We then extracted the immune-related mRNA and lncRNA expression profiles. Based on the expression profiles of immune-related lncRNAs, we identified a nine-lncRNA signature that was related to the progression of HCC. The risk score was calculated based on the expression level of the nine lncRNAs of each sample, which divided patients into high-risk and low-risk groups. We found that the increased risk score was associated with a poor prognosis of HCC patients. To assess the accuracy of the survival model, we calculated a receiver operating characteristic (ROC) for validation. The curve showed that the area under the curve (AUC) for the risk score was 0.792. Besides, both principal component analysis (PCA) and gene set enrichment analysis (GSEA) were further used for functional annotation. We found that the distribution patterns were different between the low-risk and high-risk groups in PCA, and the underlying mechanism by which the nine lncRNAs promoted the progression of HCC involved an abnormal immune status. Finally, we analyzed the infiltration of twenty-nine kinds of immune cells and the activation of immune function in HCC using the ssGSEA algorithm. The results showed that aDCs, iDCs, macrophages, Tfh, Th1, Treg, and NK cells were correlated with the progress of HCC patients. And the immune functions including APC costimulation, CCR, check point, HLA, MHC class I, and Type II IFN responses were also significantly different between the high-risk and low-risk groups. In conclusion, our study identified a nine-lncRNA signature with potential prognostic value for patients with HCC, which could be used as a new biomarker for the diagnosis and immunotherapy of HCC.
肝细胞癌 (HCC) 在常见癌症中排名第五，是全球癌症相关死亡的第二大主要原因。本研究旨在鉴定一种免疫相关的长链非编码 RNA (lncRNA) 特征作为具有预后价值的潜在生物标志物，以改善 HCC 患者的早期诊断并提供潜在的治疗靶点。本研究的对象是从癌症基因组图谱 (TCGA) 数据库下载的具有完整转录组数据和临床信息的 HCC 样本。然后，我们提取了免疫相关的 mRNA 和 lncRNA 表达谱。基于免疫相关 lncRNA 的表达谱，我们确定了一个与 HCC 进展相关的九种 lncRNA 特征。根据每个样本中九种 lncRNA 的表达水平计算风险评分，将患者分为高风险和低风险组。我们发现，风险评分的增加与 HCC 患者的预后不良相关。为了评估生存模型的准确性，我们计算了验证的接收者操作特征 (ROC)。该曲线表明，风险评分的曲线下面积 (AUC) 为 0.792。此外，还进一步使用主成分分析 (PCA) 和基因集富集分析 (GSEA) 进行功能注释。我们发现，在 PCA 中，低风险和高风险组之间的分布模式不同，九种 lncRNA 促进 HCC 进展的潜在机制涉及异常的免疫状态。最后，我们使用 ssGSEA 算法分析了 HCC 中 29 种免疫细胞的浸润和免疫功能的激活。结果表明，aDCs、iDCs、巨噬细胞、Tfh、Th1、Treg 和 NK 细胞与 HCC 患者的进展相关。并且在高风险和低风险组之间，APC 共刺激、CCR、检查点、HLA、MHC I 类和 II 型 IFN 反应等免疫功能也有显著差异。总之，本研究确定了一种具有潜在预后价值的 HCC 患者九种 lncRNA 特征，可作为 HCC 诊断和免疫治疗的新生物标志物。
