Cao Jincheng, Xu Yanni, Liu Xiaodi, Cai Yan, Luo Baoming
Department of Ultrasound, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, China.
Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Medical Research Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, China.
Heliyon. 2022 Aug 14;8(8):e10215. doi: 10.1016/j.heliyon.2022.e10215. eCollection 2022 Aug.
Hepatocellular carcinoma (HCC) remains a major tumoral burden globally, and its heterogeneity encumbers prognostic prediction. The lymphangiogenesis-related long non-coding RNAs (lrlncRNAs) reported to be implicated in immune response regulation show potential importance in predicting the prognostic and therapeutic outcome. Hence, this study aims to establish a lrlncRNA pairs-based signature not requiring specific expression levels of transcripts, which displays promising clinical practicality and satisfactory predictive capability.
Transcriptomic and clinical information of the Liver Hepatocellular Carcinoma (LIHC) project retrieved from the TCGA portal were used to find differently expressed lrlncRNA (DElrlncRNA) via analysis performed between lymphangiogenesis-related genes (lr-genes) and lncRNAs(lrlncRNA), and to ultimately construct the signature based on lrlncRNA pairs screened out via Lasso and Cox regression analyses. Akaike information criterion (AIC) values were computed to find the cut-off point optimum for high-risk and low-risk group allocation. The signature then underwent trials in terms of its predictive value for survival, clinicopathological features, immune cells infiltration in tumoral microenvironment, selected checkpoint biomarkers and chemosensitivity.
A novel lymphangiogenesis-related lncRNA pair signature was established using nine lrlncRNA pairs identified and significantly related to overall survival, clinicopathological features, immune cells infiltration and susceptibility to chemotherapy. Moreover, the signature efficacy was verified in acknowledged clinicopathological subgroups and partially validated by qRT-PCR assay in various human HCC cell lines.
The novel lrlncRNA-pairs based signature was shown to effectively and independently estimate HCC prognosis and help screen patients suitable for anti-tumor immunotherapy and chemotherapy.
肝细胞癌（HCC）仍是全球主要的肿瘤负担，其异质性阻碍了预后预测。据报道，与淋巴管生成相关的长链非编码RNA（lrlncRNAs）参与免疫反应调节，在预测预后和治疗结果方面显示出潜在的重要性。因此，本研究旨在建立一种基于lrlncRNA对的特征，该特征不需要转录本的特定表达水平，具有良好的临床实用性和令人满意的预测能力。
从TCGA数据库获取肝细胞癌（LIHC）项目的转录组和临床信息，通过对淋巴管生成相关基因（lr-genes）和lncRNAs（lrlncRNA）进行分析，找出差异表达的lrlncRNA（DElrlncRNA），并最终基于通过Lasso和Cox回归分析筛选出的lrlncRNA对构建特征。计算赤池信息准则（AIC）值，以找到高风险和低风险组分配的最佳截断点。然后对该特征在生存预测价值、临床病理特征、肿瘤微环境中的免疫细胞浸润、选定的检查点生物标志物和化疗敏感性方面进行试验。
利用鉴定出的9对与总生存、临床病理特征、免疫细胞浸润和化疗敏感性显著相关的lrlncRNA对，建立了一种新的淋巴管生成相关lncRNA对特征。此外，该特征的有效性在公认的临床病理亚组中得到验证，并在各种人HCC细胞系中通过qRT-PCR分析得到部分验证。
基于lrlncRNA对的新特征被证明能有效且独立地评估HCC预后，并有助于筛选适合抗肿瘤免疫治疗和化疗的患者。
