基于机器学习的集成算法构建新型 lncRNA 衍生免疫基因评分模型预测 HCC 患者生存

Development of a novel lncRNA-derived immune gene score using machine learning-based ensembles for predicting the survival of HCC.

机构信息

Department of Infectious Diseases and Liver Diseases, Ningbo Medical Center Lihuili Hospital, Affiliated Lihuili Hospital of Ningbo University, 1111 Jiangnan Rd., Ningbo, 315100, China.

College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, 150036, Heilongjiang, China.

出版信息

J Cancer Res Clin Oncol. 2024 Feb 9;150(2):86. doi: 10.1007/s00432-024-05608-6.

DOI:10.1007/s00432-024-05608-6

PMID:38334792

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10858126/

Abstract

BACKGROUND

Long noncoding RNAs (lncRNAs) are implicated in the tumor immunology of hepatocellular carcinoma (HCC).

METHODS

HCC mRNA and lncRNA expression profiles were used to extract immune-related genes with the ImmPort database, and immune-related lncRNAs with the ImmLnc algorithm. The MOVICS package was used to cluster immune-related mRNA, immune-related lncRNA, gene mutation and methylation data on HCC from the TCGA. GEO and ICGC datasets were used to validate the model. Data from single-cell sequencing was used to determine the expression of genes from the model in various immune cell types.

RESULTS

With this model, the area under the curve (AUC) for 1-, 3- and 5-year survival of HCC patients was 0.862, 0.869 and 0.912, respectively. Single-cell sequencing showed EREG was significantly expressed in a variety of immune cell types. Knockdown of the EREG target gene resulted in significant anti-apoptosis, pro-proliferation and pro-migration effects in HepG2 and HUH7 cells. Moreover, serum and liver tissue EREG levels in HCC patients were significantly higher than those of healthy control patients.

CONCLUSION

We built a prognostic model with good accuracy for predicting HCC patient survival. EREG is a potential immunotherapeutic target and a promising prognostic biomarker.

摘要

背景

长链非编码 RNA（lncRNA）参与了肝细胞癌（HCC）的肿瘤免疫学。

方法

利用 ImmPort 数据库提取 HCC mRNA 和 lncRNA 表达谱中的免疫相关基因，利用 ImmLnc 算法提取免疫相关 lncRNA。使用 MOVICS 包对来自 TCGA、GEO 和 ICGC 数据集的 HCC 的免疫相关 mRNA、免疫相关 lncRNA、基因突变和甲基化数据进行聚类。验证模型使用了来自单细胞测序的数据，以确定模型中基因在各种免疫细胞类型中的表达。

结果

该模型对 HCC 患者 1 年、3 年和 5 年生存率的 AUC 分别为 0.862、0.869 和 0.912。单细胞测序显示，EREG 在多种免疫细胞类型中均有显著表达。敲低 EREG 的靶基因，在 HepG2 和 HUH7 细胞中导致明显的抗凋亡、促增殖和促迁移作用。此外，HCC 患者的血清和肝组织 EREG 水平明显高于健康对照患者。