Abstract
Hepatocellular carcinoma (HCC) is a leading cause of cancer death worldwide, accounting for over 700,000 deaths each year. The lack of predictive and prognostic biomarkers for HCC, with effective therapy, remains a significant challenge for HCC management. Long non-coding RNAs (lncRNAs) play a key role in tumorigenesis and have clinical value as potential biomarkers in the early diagnosis and prediction of HCC. Jun activation domain-binding protein 1 (Jab1, also known as COP9 signalosome subunit 5, CSN5) is a potential oncogene that plays a critical role in the occurrence of HCC. Here, we performed a comprehensive analysis for Jab1/CSN5-associated lncRNAs to predict the prognosis of HCC. The differentially expressed (DE) lncRNAs between in HCC were analyzed based on the TCGA RNA-seq data. We detected 1031 upregulated lncRNAs in 371 HCC tissues and identified a seven-lncRNA signature strongly correlated with Jab1/CSN5 (SNHG6, CTD3065J16.9, LINC01604, CTD3025N20.3, KB-1460A1.5, RP13-582O9.7, and RP11-29520.2). We further evaluated the prognostic significance of these lncRNAs by GEPIA (http://gepia.cancer-pku.cn/). The expression data in 364 liver tumors indicated that this seven-lncRNA signature could better predict worse survival in HCC patients. Moreover, 35 clinical HCC samples were evaluated to assess the validity and reproducibility of the bioinformatic analysis. We found that the targeted lncRNAs were upregulated, with a strong association with Jab1/CSN5 and prognostic value in HCC. Functional enrichment analysis by Gene Ontology (GO) showed that these seven prognostic lncRNAs exhibit oncogenic properties and are associated with prominent hallmarks of cancer. Overall, our findings demonstrate the clinical implication of Jab1/CSN5 with the seven‐lncRNAs in predicting survival for patients with HCC.
Highlights
Hepatocellular carcinoma (HCC) is the second leading cause of death related to cancer among males and the sixth among females, accounting for over 700,000 deaths each year worldwide [1]
We identified seven-Long non-coding RNAs (lncRNAs) signature from The Cancer Genome Atlas (TCGA) liver hepatocellular carcinoma (LIHC) dataset with clinical validations and determined its prognostic value was independent of clinical factors
Seven lncRNAs were upregulated in HCC tissue specimens and correlated with poor outcome By testing and analyzing the relative expression level of sevenlncRNA signature and Jab1/CSN5 in 35 paired HCC tissues and adjacent normal hepatic tissues collecting from Zhongnan Hospital (Fig. 4), we found that Jab1/CSN5 was remarkably overexpressed in HCC compared with adjacent normal tissues (P < 0.01), as well as SNGH6, CTD3025N20.3, KB-1460A1.5, RP13582O9.7, and RP11-29520.2 (Fig. 4A)
Summary
Hepatocellular carcinoma (HCC) is the second leading cause of death related to cancer among males and the sixth among females, accounting for over 700,000 deaths each year worldwide [1]. Prevention, early detection, and treatment improve cancer outcomes; the incidence of cancer mortality continues to rise in most HCC patients with a 5-year survival rate is still below 50% [2]. The level of exposure to environmental and infectious risk factors with early detection are the leading causes of the variation seen in liver cancer incidence and mortality [3]. Several studies have recently demonstrated the role of lncRNAs in diverse biological processes, including the regulation of epigenetic inheritance, transcriptional and post-transcriptional levels, imprinting, apoptosis, and drug resistance, and tumorigenesis via directly or indirectly regulating related PCGs (protein-coding genes) [6,7,8,9,10]. Several lncRNAs, including HOTAIR, HULC, and HOTTIP, are directly involved in tumorigenesis and metastasis in HCC [13,14,15]
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