Abstract
BackgroundAlthough the effects of macrophages and CD8 T cell infiltration on clinical outcome have been widely reported, the association between immunity-associated gene with them for hepatocellular carcinoma (HCC) remains unclear.Materials and methodsThe ssGSEA served for quantifying the macrophages as well as CD8 T cell infiltration in the HCC samples obtained from TCGA database. Kaplan–Meier (KM) survival assay was used to determine the associations between macrophages and CD8 T cell infiltration with OS. LASSO Cox regressive method assisted in developing an immune gene signature as well as building a risk score. The performance was evaluated by the time-dependent ROC together with the KM survival analysis. The ICGC database were adopted for external verification. CIBERSORT was applied to the correlation analysis on the immune-related signature and the immunocyte infiltration. GSEA were employed exploring the underlying molecular mechanisms.ResultsIncreased CD8+ T cell infiltration was associated with longer OS, whereas a greater infiltration of macrophages was related to shorter OS. There were 398 differential expression genes (DEGs) between the high- and low infiltration groups with the “edgeR” package. An prognostic signature consisted of 10 immune genes was built in TCGA and examined in ICGC. The uniform cutoff (0.927) was adopted for separating sufferers into the high-risk (HR) and low-risk (LR) groups. The ROC curves revealed that the AUC data for this signature predicting 1, 2, 3, 4 and 5 year were all above 0.7 in both TCGA and ICGC cohort and patients in the HR group exhibited an evidently weaker prognostic results compared with the LR group. The HR group presented evidently greater Tregs and Macrophage M0 relative to the LR group, whereas the LR group saw the enrichment of CD8 T cells.ConclusionThe immune signature associated with macrophages as well as CD8 T cell infiltration has reliable prognostic and predictive value for HCC patients.
Highlights
The effects of macrophages and CD8 T cell infiltration on clinical outcome have been widely reported, the association between immunity-associated gene with them for hepatocellular carcinoma (HCC) remains unclear
Increased CD8+ T cell infiltration was associated with longer Overall survival (OS), whereas a greater infiltration of macrophages was related to shorter OS
The Receiver operating characteristic (ROC) curves revealed that the Area under curve (AUC) data for this signature predicting 1, 2, 3, 4 and 5 year were all above 0.7 in both The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) cohort and patients in the HR group exhibited an weaker prognostic results compared with the LR group
Summary
The effects of macrophages and CD8 T cell infiltration on clinical outcome have been widely reported, the association between immunity-associated gene with them for hepatocellular carcinoma (HCC) remains unclear. Hepatocellular carcinoma (HCC) is a typical primary hepatoma, occupying 85–90% of the total number. It ranks six among all the malignant tumor types. Because of there are no obvious symptoms in the early period of the onset of HCC, the majority of sufferers were in the middle and late period during the diagnosis [2], and missed the best opportunity for treatment, so the survival time was short and the prognosis was poor. There are still many deficiencies in the traditional clinical indicators for HCC risk stratification and monitoring, which can not effectively guide patients to individualized targeted therapy. It is urgent to develop more reliable methods to evaluate the prognosis of HCC in order to guide clinical individualized treatment
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