Abstract
Hepatocellular carcinoma (HCC) is one of the main causes of cancer deaths globally. Immunotherapy is becoming increasingly important in the cure of advanced HCC. Thus it is essential to identify biomarkers for treatment response and prognosis prediction. We searched publicly available databases and retrieved 465 samples of genes from The Cancer Genome Atlas (TCGA) database and 115 tumor samples from Gene Expression Omnibus (GEO). Meanwhile, we used the ImmPort database to determine the immune-related genes as well. Weighted gene correlation network analysis, Cox regression analysis and least absolute shrinkage and selection operator (LASSO) analysis were used to identify the key immune related genes (IRGs) which are closely related to prognosis. Gene set enrichment analysis (GSEA) was implemented to explore the difference of Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway between Immune high- and low-risk score groups. Finally, we made a prognostic nomogram including Immune-Risk score and other clinicopathologic factors. A total of 318 genes from prognosis related modules were identified through weighted gene co-expression network analysis (WGCNA). 46 genes were strongly linked to prognosis after univariate Cox analysis. We constructed a seven genes prognostic signature which showed powerful prediction ability in both training cohort and testing cohort. 16 significant KEGG pathways were identified between high- and low- risk score groups using GSEA analysis. This study identified and verified seven immune-related prognostic biomarkers for the patients with HCC, which have potential value for immune modulatory and therapeutic targets.
Highlights
Hepatocellular carcinoma (HCC) is one of the main causes of cancer deaths globally
Genes from the significant prognostic-related modules were further computed for Cox regression and Lasso regression and constructed an immune related genes (IRGs) prognostic signature consisting of seven genes (NR1D1, Hepatoma-derived growth factor (HDGF), LMBR1, PRDX1, NR6A1, EPO and Deoxycytidine kinase (DCK))
The highest correlation with survival status was shown in green module while the red and blue modules showed the highest correlation with the overall survival of HCC patients (Fig. 2D)
Summary
Hepatocellular carcinoma (HCC) is one of the main causes of cancer deaths globally. Immunotherapy is becoming increasingly important in the cure of advanced HCC. While most HCC patients were already at advanced status when received the diagnoses and were not amenable to curative resection or ablation Palliative treatments such as: trans-arterial approaches and systemic therapies are important for such p atients[5]. According to the 2020 American Society of Clinical Oncology guideline, Atezolizumab + bevacizumab has been recommended as the new first-line treatment for most advanced HCC patients[11] This management has shown superior efficacy including higher objective response rates and median survival compared with sorafenib based on a global, open-label, phase 3 trial[12].
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