Profiles of prognostic alternative splicing signature in hepatocellular carcinoma

Abstract

Previous studies have demonstrated the role of abnormal alternative splicing (AS) in tumor progression. This study examines the prognostic index (PI) of alternative splices (ASs) in patients with hepatocellular carcinoma (HCC). The clinical features and splicing events of patients with HCC were downloaded from The Cancer Genome Atlas (TCGA). Differentially expressed AS (DEAS) were compared between HCC and adjacent normal samples. Univariate Cox regression analysis was used to determine changes in DEAS associated with overall survival (OS). A PI was generated from OS‐associated DEASs using Kaplan‐Meier curves, receiver operating characteristic (ROC) curves, multivariate Cox regression, and cluster analysis. Then, the correlation between DEASs and splicing factors was assessed, followed by functional and pathway enrichment analysis. We identified 34 163 ASs of 8985 genes in HCC, and 153 OS‐ASs were identified using univariate Cox regression analysis. Low‐ and high‐PI groups were determined based on the median “PI‐ALL” value according to significantly different survival (P = 2.2e − 16). The ROC curve of all PI (PI‐ALL) had an area under the curve (AUC) of 0.993 for survival status in patients with HCC. A potential regulatory network associated with prognosis of patients with HCC was established. Enrichment analysis also resulted in the identification of several pathways potentially associated with carcinogenesis and progression of HCC. Four clusters were identified that were associated with clinical features and prognosis. Our study generated comprehensive profiles of ASs in HCC. The interaction network and functional connections were used to elucidate the underlying mechanisms of AS in HCC.

Systematic Analysis of Alternative Splicing Landscape in Pancreatic Adenocarcinoma Reveals Regulatory Network Associated with Tumorigenesis and Immune Response

“…The majority of favorable prognostic AS events (HR <1) were upregulated by SFs, whereas adverse AS events (HR >1) were downregulated. In contrast to observations in other cancers, this suggests that most of the SFs in PDAC inhibit tumor progression through the regulation of AS events [ 53 , 54 ]. However, owing to the lack of normal samples in TCGA, we were unable to identify differentially expressed SFs and draw comprehensive conclusions about the effects of SFs on PDAC.…”

Integrative analysis identifies key mRNA biomarkers for diagnosis, prognosis, and therapeutic targets of HCV-associated hepatocellular carcinoma

“…Recently, a growing number of candidate biomarkers for diagnosis or prognosis of HCC have been identified [ 3 – 12 ], among which the most commonly reported biomarkers are dysregulated genes [ 3 , 6 , 11 ], significant members of a certain gene family or gene set [ 4 , 10 ], potential CpG methylation status [ 7 , 9 ], and alternative splicing signatures [ 5 , 12 ]. For example, a 24-mRNA-based risk signature has been developed as an independent risk classifier for the prediction of early recurrence in HCC patients [ 6 ].…”

Systemic characterization of alternative splicing related to prognosis and immune infiltration in malignant mesothelioma

“…Recent studies have focused on investigating the survival prognostic value of AS in cancers. Numerous studies have conducted SpliceSeq analyses to generate AS profiles for cancer prognosis monitoring with scores, including papillary thyroid carcinoma [ 39 ], colorectal cancer [ 40 ], non-small cell lung cancer [ 41 ], melanoma [ 42 ], hepatocellular carcinoma [ 43 ] and kidney cancer [ 44 ]. Our study added to the comprehensive understanding of patients with MM and identified survival-related AS signatures using high-throughput data.…”