Abstract
Background Ubiquitin-specific protease 39 is mainly involved in mRNA splicing and multiple kinds of tumors. Accumulating evidence has shown that USP39 participated in the proliferation and metastasis of hepatocellular carcinoma (HCC). The present study aimed to demonstrate the association between USP39 expression and clinical features and the diagnostic value in HCC based on the Cancer Genome Atlas (TCGA). Methods A comprehensive analysis for expression of USP39 in HCC was conducted by using multiple databases. The mRNA level of USP39, clinical features, survival rate, and diagnostic value in HCC were analyzed using data from TCGA. The Gene Set Enrichment Analysis (GSEA) was conducted to analyze signaling pathways correlated with USP39 expression in HCC. Results The mRNA level of USP39 was significantly elevated in HCC. The expression of USP39 showed significant correlation with T stage, pathologic stage, tumor status, age, and histologic grade. Logistic analysis demonstrated that high expression of USP39 was significantly associated with older age, tumor status, advanced pathologic stage, T stage, and higher histologic grade. Univariate Cox regression analysis showed that high expression of USP39 was significantly associated with advanced T stage, pathological stage, and tumor status. Multivariate Cox analysis confirmed the result that USP39 expression was an independent prognostic factor for overall survival (OS) in HCC. Results of Kaplan–Meier curves showed that high expression of USP39 had a significant association with poor OS, disease-free survival (DSS), and progress-free interval (PFI) in HCC. ROC analysis indicated that USP39 could be regarded as a promising marker for distinguishing HCC from nontumor. Conclusion The increased USP39 might play roles in the progression, diagnosis, and prognosis of HCC.
Highlights
Hepatocellular carcinoma (HCC), mainly induced by a hepatitis virus infection, alcoholic consumption, or other liver diseases, is still among the most common malignancies worldwide. e 2018 global cancer statistics showed that the number of annual cases of hepatocellular carcinoma (HCC) worldwide was 841,000, ranking sixth in the incidence spectrum of malignant tumors
A fold change of 1.5, P < 0.05, and a gene rank in the top 10% were considered to indicate a statistically significant difference. e P value was calculated using Student’s t-test. e Human Protein Atlas (HPA) [14] is an open-access online database containing the pathology data for exploration of the human proteome. e level of USP39 protein in liver cancers and normal liver tissues was obtained from the HPA. e publicly open-access database the Cancer Genome Atlas (TCGA) was used to explore the expression of USP39 in HCC. e mRNA expression dataset with a total of 424 samples (Type: RNA-Seq FPKM) and the corresponding clinical information in TCGA were included
Pooled analysis in the Oncomine database showed that USP39 was significantly overexpressed in HCC (P 5.18e − 4, Figure 1(c))
Summary
Hepatocellular carcinoma (HCC), mainly induced by a hepatitis virus infection, alcoholic consumption, or other liver diseases, is still among the most common malignancies worldwide. e 2018 global cancer statistics showed that the number of annual cases of HCC worldwide was 841,000, ranking sixth in the incidence spectrum of malignant tumors. E mRNA level of USP39, clinical features, survival rate, and diagnostic value in HCC were analyzed using data from TCGA. E Gene Set Enrichment Analysis (GSEA) was conducted to analyze signaling pathways correlated with USP39 expression in HCC. E expression of USP39 showed significant correlation with T stage, pathologic stage, tumor status, age, and histologic grade. Logistic analysis demonstrated that high expression of USP39 was significantly associated with older age, tumor status, advanced pathologic stage, T stage, and higher histologic grade. Univariate Cox regression analysis showed that high expression of USP39 was significantly associated with advanced T stage, pathological stage, and tumor status. Results of Kaplan–Meier curves showed that high expression of USP39 had a significant association with poor OS, disease-free survival (DSS), and progress-free interval (PFI) in HCC. Conclusion. e increased USP39 might play roles in the progression, diagnosis, and prognosis of HCC
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