Construction of a prognostic model based on nine immune-related genes and identification of small molecule drugs for hepatocellular carcinoma (HCC)

This study aimed to develop a prognostic model for hepatocellular carcinoma (HCC) based on immune-related genes and to identify new potential small-molecule drugs. A differential gene expression analysis of high-throughput microarray data from The Cancer Genome Atlas (TCGA) was performed to identify immune-related genes. By comparison with an immune-related genome, nine genes with important prognostic value for HCC were identified. The prognostic characteristics were established based on univariate and multivariate COX and Lasso regression analyzes. Subsequently, immune-related HCC risk signatures were constructed based on these identified nine immune-related genes and patients were classified as being at high or low risk according to these signatures. The overall survival (OS) time of high-risk patients was significantly shorter than that of low-risk patients. When studied as an independent prognostic factor of HCC, the significant prognostic value of this feature can be seen in the stratified cohorts. For clinical application, it was developed a nomogram that includes nine clinical risk factors and the prognostic model built based on the identified immune-related genes. Internal and external verification on 243 HCC tissues through International Cancer Genome Consortium (ICGC) database were performed to make this model more accurate and reliable. In addition, it was observed a positive regulation between the identified immune-related genes and their transcription factors found in HCC patients. Moreover, physiological function and signaling pathway of identified immune-related genes were studied by GO and KEGG enrichment analysis. Finally, several new small molecular drugs with potential for the treatment of HCC have been identified in the CMap database.