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

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

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.

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.

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