Abstract
BackgroundHepatocellular carcinoma (HCC) is one of the most common malignant tumors in the world, and its 5-year survival rate is less than 20%, despite various treatments being available. Increasing evidence indicates that alternative splicing (AS) plays a nonnegligible role in the formation and development of the tumor microenvironment (TME). However, the comprehensive analysis of the impact on prognostic AS events on immune-related perspectives in HCC is lacking but urgently needed.MethodsThe transcriptional data and clinical information of HCC patients were downloaded from TCGA (The Cancer Genome Atlas) database for calculating immune and stromal scores by ESTIMATE algorithm. We then divided patients into high/low score groups and explored their prognostic significance using Kaplan–Meier curves. Based on stromal and immune scores, differentially expressed AS events (DEASs) were screened and evaluated with functional enrichment analysis. Additionally, a risk score model was established by applying univariate and multivariate Cox regression analyses. Finally, gene set variation analysis (GSVA) was adopted to explore differences in biological behaviors between the high- and low-risk subgroups.ResultsA total of 370 HCC patients with complete and qualified corresponding data were included in the subsequent analysis. According to the results of ESTIMATE analysis, we observed that the high immune/stromal score group had a longer survival probability, which was significantly correlated with prognosis in HCC patients. In addition, 467 stromal/immune score-related DEASs were identified, and enrichment analysis revealed that DEASs were significantly enriched in pathways related to HCC tumorigenesis and the immune microenvironment. More importantly, the final prognostic signature containing 16 DEASs showed powerful predictive ability. Finally, GSVA demonstrated that activation of carcinogenic pathways and immune-related pathways in the high-risk group may lead to poor prognosis.ConclusionsCollectively, these outcomes revealed prognostic AS events related to carcinogenesis and the immune microenvironment, which may yield new directions for HCC immunotherapy.
Highlights
Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in the world, and its 5-year survival rate is less than 20%, despite various treatments being available
According to ESTIMATE analysis, immune scores were distributed between − 861.77 and 3157.28, and stromal scores ranged from − 1622.33 to 1180.26
Kaplan–Meier survival curves showed that the high immune score group had a longer survival probability than the low immune score group (P = 0.0076); patients with a high stromal score had a longer survival probability (P = 0.0026) (Fig. 2a, b)
Summary
Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in the world, and its 5-year survival rate is less than 20%, despite various treatments being available. The comprehensive analysis of the impact on prognostic AS events on immune-related perspectives in HCC is lacking but urgently needed. Hepatocellular carcinoma (HCC) is the fourth most common cause of cancer-related deaths, ranking sixth in new cancer cases worldwide (Villanueva and Longo 2019). Treatment of HCC remains surgery-based comprehensive treatment, but most patients are usually diagnosed in a late stage due to a lack of typical clinical manifestations in early HCC (Heimbach et al 2018; Bruix and Sherman 2011). Patients with HCC are in urgent need of newer and more effective treatments
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