Yin Lu, Zhou Liuzhi, Gao Shiqi, Feng Yina, Zhu Hanzhang, Xiang Jingjing, Xu Rujun
Department of Pathology, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Department of Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Front Mol Biosci. 2022 Feb 4;9:807418. doi: 10.3389/fmolb.2022.807418. eCollection 2022.
HCC is one of the most common types of malignancies worldwide and the fourth-leading cause of cancer deaths. Thus, there is an urgent need to search for novel targeted therapies in HCC. 186 m6a-related lncRNAs were screened for subsequent analysis. Two distinct m6A modification clusters were identified to be associated with the overall prognosis in TCGA-LIHC based on the m6A-related lncRNAs profiling, followed by univariate Cox regression analysis. In addition, four m6A-related lncRNAs prognostic signatures were developed and validated that could predict the OS of HCC patients, followed by univariate Cox regression, LASSO regression, and multivariate Cox regression analysis. Moreover, four m6A-related lncRNAs were identified to be related to HCC prognosis. ESTIMATE was used to evaluate the stromal score, immune score, ESTIMATE score, and tumor purity of each HCC sample. ssGSEA was performed to identify the enrichment levels of 29 immune signatures in each sample. Finally, quantitative real-time polymerase chain reaction shown that KDM4A-AS1, BACE1-AS, and NRAV expressions were upregulated in HCC patients. We proved that our m6A-related lncRNAs signature had powerful and robust ability for predicting OS of different HCC subgroups.
肝癌是全球最常见的恶性肿瘤类型之一，也是癌症死亡的第四大主要原因。因此，迫切需要在肝癌中寻找新的靶向治疗方法。筛选了186个与m6A相关的长链非编码RNA用于后续分析。基于与m6A相关的长链非编码RNA谱，在TCGA-LIHC中鉴定出两个不同的m6A修饰簇与总体预后相关，随后进行单变量Cox回归分析。此外，开发并验证了四个与m6A相关的长链非编码RNA预后特征，可预测肝癌患者的总生存期，随后进行单变量Cox回归、LASSO回归和多变量Cox回归分析。此外，鉴定出四个与m6A相关的长链非编码RNA与肝癌预后相关。使用ESTIMATE评估每个肝癌样本的基质评分、免疫评分、ESTIMATE评分和肿瘤纯度。进行单样本基因集富集分析（ssGSEA）以确定每个样本中29种免疫特征的富集水平。最后，定量实时聚合酶链反应显示，肝癌患者中KDM4A-AS1、BACE1-AS和NRAV的表达上调。我们证明，我们的与m6A相关的长链非编码RNA特征对预测不同肝癌亚组的总生存期具有强大而稳健的能力。
