基于外泌体相关免疫抑制基因与肝癌肿瘤微环境的综合研究。
A comprehensive study based on exosome-related immunosuppression genes and tumor microenvironment in hepatocellular carcinoma.
机构信息
Department of Hepatobiliary Surgery, The First Affiliated Hospital of Wenzhou Medical University, No.2 fuxue lane, Wenzhou, 325000, Zhejiang, China.
出版信息
BMC Cancer. 2022 Dec 22;22(1):1344. doi: 10.1186/s12885-022-10463-0.
BACKGROUND
Exosomes play an important role in the tumor microenvironment (TME) and the mechanisms of tumor immune escape in hepatocellular carcinoma (HCC). It is known that immunosuppressive genes, involved in the processes of tumor immunosuppression, are associated with cancer progression. This study aimed to explore the prognostic values of exosome-related immunosuppression genes (ERIGs) in HCC.
METHODS
The RNA-seq transcriptome data of 374 HCC patients were obtained from the Cancer Genome Atlas (TCGA) database. The TCGA cohort was randomly divided into the training cohort and validation cohort in a 1:1 ratio. WGCNA analysis and Pearson correlation analysis were used to identify ERIGs. The Lasso regression method was used to construct a 5-ERIG signature. The prognostic value of our signature was examined in the First Affiliated Hospital of Wenzhou Medical University (FAHWMU) cohort.
RESULTS
Univariate Cox regression analysis was used to screen prognostic ERIGs. Subsequently, these prognostic ERIGs were included in Lasso regression analyses to identify 5 key ERIGs (ASAP1, IARS1, GTF3C2, TPD5L2 and SLC52A2) and construct a 5-ERIG signature. The patients in the low-risk group had better prognosis than those in the high-risk group. Univariate and multivariate cox regression revealed that risk score was an independent prognostic risk factor of HCC. Gene set enrichment analysis (GSEA) showed that this signature was highly associated with TME-related pathways. Subsequent analyses revealed the potential role of the signature in regulating the TME in HCC. In addition, a lower immunotherapy score was found in patients with high risk-score. Of note, this signature was confirmed to have a good performance in predicting HCC prognosis in the FAHWMU cohort. Moreover, knockdown of 5 ERIGs of this signature contributed to the suppression the Hep3B cell proliferation.
CONCLUSIONS
We generated a novel prognostic 5-ERIG signature to accurately predict the prognosis of patients with HCC, and this signature may serve as an indicator of immunotherapy for HCC.
背景
外泌体在肿瘤微环境（TME）和肝癌（HCC）的肿瘤免疫逃逸机制中发挥重要作用。已知参与肿瘤免疫抑制过程的免疫抑制基因与癌症进展有关。本研究旨在探讨 HCC 中外泌体相关免疫抑制基因（ERIGs）的预后价值。
方法
从癌症基因组图谱（TCGA）数据库中获取 374 例 HCC 患者的 RNA-seq 转录组数据。TCGA 队列按 1:1 比例随机分为训练队列和验证队列。采用 WGCNA 分析和 Pearson 相关性分析鉴定 ERIGs。使用 Lasso 回归方法构建 5-ERIG 特征。在温州医科大学第一附属医院（FAHWMU）队列中检验我们特征的预后价值。
结果
单因素 Cox 回归分析筛选预后 ERIGs。随后，这些预后 ERIGs 被纳入 Lasso 回归分析，以确定 5 个关键 ERIGs（ASAP1、IARS1、GTF3C2、TPD5L2 和 SLC52A2）并构建 5-ERIG 特征。低风险组患者的预后优于高风险组患者。单因素和多因素 Cox 回归表明风险评分是 HCC 的独立预后危险因素。基因集富集分析（GSEA）表明，该特征与 TME 相关途径高度相关。后续分析表明该特征在调节 HCC 的 TME 中具有潜在作用。此外，高风险评分患者的免疫治疗评分较低。值得注意的是，该特征在 FAHWMU 队列中被证实能够很好地预测 HCC 预后。此外，该特征的 5 个 ERIGs 的敲低有助于抑制 Hep3B 细胞的增殖。
结论
我们生成了一个新的预后 5-ERIG 特征，可准确预测 HCC 患者的预后，该特征可能作为 HCC 免疫治疗的指标。
Zotero 插件