鉴定与肝细胞癌免疫微环境相关的预后可变剪接事件。
Identification of prognostic alternative splicing events related to the immune microenvironment of hepatocellular carcinoma.
机构信息
Department of Chemoradiation Oncology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People's Republic of China.
Department of Obstetrics and Gynecology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People's Republic of China.
出版信息
Mol Med. 2021 Apr 8;27(1):36. doi: 10.1186/s10020-021-00294-3.
BACKGROUND
Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in the world, and its 5-year survival rate is less than 20%, despite various treatments being available. Increasing evidence indicates that alternative splicing (AS) plays a nonnegligible role in the formation and development of the tumor microenvironment (TME). However, the comprehensive analysis of the impact on prognostic AS events on immune-related perspectives in HCC is lacking but urgently needed.
METHODS
The transcriptional data and clinical information of HCC patients were downloaded from TCGA (The Cancer Genome Atlas) database for calculating immune and stromal scores by ESTIMATE algorithm. We then divided patients into high/low score groups and explored their prognostic significance using Kaplan-Meier curves. Based on stromal and immune scores, differentially expressed AS events (DEASs) were screened and evaluated with functional enrichment analysis. Additionally, a risk score model was established by applying univariate and multivariate Cox regression analyses. Finally, gene set variation analysis (GSVA) was adopted to explore differences in biological behaviors between the high- and low-risk subgroups.
RESULTS
A total of 370 HCC patients with complete and qualified corresponding data were included in the subsequent analysis. According to the results of ESTIMATE analysis, we observed that the high immune/stromal score group had a longer survival probability, which was significantly correlated with prognosis in HCC patients. In addition, 467 stromal/immune score-related DEASs were identified, and enrichment analysis revealed that DEASs were significantly enriched in pathways related to HCC tumorigenesis and the immune microenvironment. More importantly, the final prognostic signature containing 16 DEASs showed powerful predictive ability. Finally, GSVA demonstrated that activation of carcinogenic pathways and immune-related pathways in the high-risk group may lead to poor prognosis.
CONCLUSIONS
Collectively, these outcomes revealed prognostic AS events related to carcinogenesis and the immune microenvironment, which may yield new directions for HCC immunotherapy.
背景
肝细胞癌（HCC）是世界上最常见的恶性肿瘤之一，尽管有多种治疗方法，但 5 年生存率仍低于 20%。越来越多的证据表明，可变剪接（AS）在肿瘤微环境（TME）的形成和发展中起着不可忽视的作用。然而，全面分析对免疫相关方面有影响的预后 AS 事件在 HCC 中的作用仍缺乏，但又急需这方面的研究。
方法
从 TCGA（癌症基因组图谱）数据库下载 HCC 患者的转录组数据和临床信息，通过 ESTIMATE 算法计算免疫和基质评分。然后，我们将患者分为高/低评分组，并通过 Kaplan-Meier 曲线探讨其预后意义。基于基质和免疫评分，筛选差异表达的 AS 事件（DEASs），并进行功能富集分析进行评估。此外，通过单因素和多因素 Cox 回归分析建立风险评分模型。最后，采用基因集变异分析（GSVA）探索高低风险亚组之间的生物学行为差异。
结果
共有 370 名 HCC 患者具有完整且合格的对应数据被纳入后续分析。根据 ESTIMATE 分析的结果，我们观察到高免疫/基质评分组的生存概率更高，这与 HCC 患者的预后显著相关。此外，确定了 467 个基质/免疫评分相关的 DEASs，富集分析表明 DEASs 显著富集在与 HCC 肿瘤发生和免疫微环境相关的途径中。更重要的是，最终包含 16 个 DEAS 的预后标志物具有强大的预测能力。最后，GSVA 表明高危组中致癌途径和免疫相关途径的激活可能导致不良预后。
结论
总之，这些结果揭示了与致癌和免疫微环境相关的预后 AS 事件，这可能为 HCC 的免疫治疗提供新的方向。
Zotero 插件