Abstract
BackgroundGrowing evidence has suggested that immune-related genes play crucial roles in the development and progression of hepatocellular carcinoma (HCC). Nevertheless, the utility of immune-related genes for evaluating the prognosis of HCC patients are still lacking. The study aimed to explore gene signatures and prognostic values of immune-related genes in HCC.MethodsWe comprehensively integrated gene expression data acquired from 374 HCC and 50 normal tissues in The Cancer Genome Atlas (TCGA). Differentially expressed genes (DEGs) analysis and univariate Cox regression analysis were performed to identify DEGs that related to overall survival. An immune prognostic model was constructed using the Lasso and multivariate Cox regression analyses. Furthermore, Cox regression analysis was applied to identify independent prognostic factors in HCC. The correlation analysis between immune-related signature and immune cells infiltration were also investigated. Finally, the signature was validated in an external independent dataset.ResultsA total of 329 differentially expressed immune‐related genes were detected. 64 immune‐related genes were identified to be markedly related to overall survival in HCC patients using univariate Cox regression analysis. Then we established a TF-mediated network for exploring the regulatory mechanisms of these genes. Lasso and multivariate Cox regression analyses were applied to construct the immune-based prognostic model, which consisted of nine immune‐related genes. Further analysis indicated that this immune-related prognostic model could be an independent prognostic indicator after adjusting to other clinical factors. The relationships between the risk score model and immune cell infiltration suggested that the nine-gene signature could reflect the status of tumor immune microenvironment. The prognostic value of this nine-gene prognostic model was further successfully validated in an independent database.ConclusionsTogether, our study screened potential prognostic immune-related genes and established a novel immune-based prognostic model of HCC, which not only provides new potential prognostic biomarkers and therapeutic targets, but also deepens our understanding of tumor immune microenvironment status and lays a theoretical foundation for immunotherapy.
Highlights
Growing evidence has suggested that immune-related genes play crucial roles in the development and progression of hepatocellular carcinoma (HCC)
A significant proportion of patients will have postoperative recurrence or distant metastasis [5]. Drugs such as sorafenib and regorafenib have been shown to be effective against advanced HCC [6, 7]
Expressed immune‐related genes and transcription factors (TFs) in HCC A total of 329 immune‐related genes (267 upregulated and 62 downregulated) and 117 TFs (108 upregulated and 9 downregulated) were identified as differentially expressed in HCC tissues compared with normal tissues
Summary
Growing evidence has suggested that immune-related genes play crucial roles in the development and progression of hepatocellular carcinoma (HCC). Hepatocellular carcinoma (HCC) accounts for 85–90% of all liver cancers and has received public attention. Despite rapid advances in new tests and treatments, the 5-year survival rate for HCC is still less than one in five [3]. Surgery is still the main treatment for early liver cancer [4]. A significant proportion of patients will have postoperative recurrence or distant metastasis [5]. Drugs such as sorafenib and regorafenib have been shown to be effective against advanced HCC [6, 7]. It is worth mentioning that patients with the same pathological type and clinical stage often have different outcomes after the same treatment, which is mainly due to the genetic heterogeneity of patients [8]
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