Development an Immune-Related MicroRNA Risk Index in Hepatocellular Carcinoma

Hepatocellular carcinoma (HC) has emerged as one of the most prevalent malignancies on a global scale. Recently, immunotherapy has achieved favorable effectiveness in the management of multiple cancers. However, there are limited therapeutic options for advanced HC. As the liver is a special immune organ, we intend to uncover potential and effective immunotherapeutic modalities for HC. Our study was designed to develop specific immune-related miRNAs (IRMs) for outcome assessment and individualized strategies for the management of HC.

The miRNA-seq and survival data of TCGA-LIHC dataset was enrolled into this program. We first collected IRMs from Immune-miR website. Differentially expression analysis was applied to screen aberrantly expressed IRMs. In order to set up an IRM-related index (IRMRI) in HC, we conducted the Cox relevant methods. Next, the statistical approaches (survival curve and ROC curve analyses) were utilized to detect the evaluation capacity of our IRMRI. Subsequently, we obtained the target genes of hub miRNAs from IRMRI through three miRNA-related predictive online tools (miRDB, miRTarBase, and TargetScan websites).

Five IRMs were determined to develop the IRMRI. It can effectively segregate all HC cases from two different risk subgroups. We identified a marked discrepancy in survival outcome between the two groups by survival analysis and confirmed the reliability of IRMRI in two testing sets. Moreover, we collected 10 hub target genes (ESR1, IGF1, PDGFRB, JUN, MYC, ZWINT, MAD2L1, TOP2A, KIF11, and CDCA8) which were strongly linked to HC progression and malignant behavior.

We screened out five hub IRMs with clinical value and constructed a risk index model in HC, which can precisely assess the risk status and outcome of patients to a certain extent.