Prognostic roles of the transcriptional expression of exportins in hepatocellular carcinoma

Abstract

Aims: A large number of studies have suggested that exportins (XPOs) play a pivotal role in human cancers. In the present study, we analyzed XPO mRNA expression in cancer tissues and explored their prognostic value in hepatocellular carcinoma (HCC). Methods: Transcriptional and survival data related to XPO expression in HCC patients were obtained through the ONCOMINE and UALCAN databases. Survival analysis plots were drawn with Gene Expression Profiling Interactive Analysis (GEPIA). Sequence alteration data for XPOs were obtained from The Cancer Genome Atlas (TCGA) database and c-BioPortal. Gene functional enrichment analyses were performed with Database for Annotation, Visualization and Integrated Discovery (DAVID). Results: Compared with normal liver tissues, significant XPO mRNA overexpression was observed in HCC cancer tissues. There was a trend of higher XPO expression in more advanced clinical stages and lower differentiated pathological grades of HCC. In HCC patients, high expression of XPO1, CSE1L, XPOT, XPO4/5/6 was related to poor overall survival (OS), and XPO1, CSE1L and XPO5/6 were correlated with poor disease-free survival (DFS). The main genetic alterations in XPOs involved mRNA up-regulation, DNA amplification and deletion. General XPO mutations were remarkably associated with worse OS and mostly affected the pathways of RNA transport and oocyte meiosis. Conclusion: High expression of XPOs was associated with a poor prognosis in HCC patients. XPOs may be exploited as good prognostic biomarkers for survival in HCC patients.

A Key mRNA-miRNA-lncRNA Competing Endogenous RNA Triple Sub-network Linked to Diagnosis and Prognosis of Hepatocellular Carcinoma

“…Therefore, we tried to establish a prognosis/diagnosis-associated mRNA-miRNA-lncRNA ceRNA triple sub-network in hepatocellular carcinoma. By performing survival (OS and RFS) analysis using TCGA hepatocellular carcinoma data, nine genes including three novel genes (CELSR3, GPSM2 and CHEK1) and six "known" genes [CLEC3B (26), DNASE1L3 (27), PTTG1 (28,29), KIF2C (30), XPO5 (31,32) and UBE2S (33,34)] were identified as prognosisassociated genes in hepatocellular carcinoma. The prognostic values of the three novel genes in hepatocellular carcinoma have not been investigated so far.…”

“…By intersecting OS-associated genes and RFSassociated genes, 9 genes (CLEC3B, DNASE1L3, PTTG1, CELSR3, GPSM2, KIF2C, XPO5, UBE2S, and CHEK1) were defined as candidate genes, which were commonly appeared in OS-associated gene set and RFS-associated gene set ( Figure 1A). After reviewing the published literatures and previous studies, we found that 6 of 9 genes [CLEC3B (26), DNASE1L3 (27), PTTG1 (28,29), KIF2C (30), XPO5 (31,32), and UBE2S (33,34)] have been demonstrated to act as promising prognostic biomarkers for hepatocellular carcinoma. The rest three genes (CELSR3, GPSM2, and CHEK1) have not been studied for their prognostic values in hepatocellular carcinoma so far.…”

Peptide:MHC dependent activation of natural killer cells through KIR2DS2 generates anti-tumor responses

“…This peptide was derived from the XPO1 (exportin-1/CRM1) protein, which is thought to function as the sole nuclear exporter for many different tumor suppressor and growth regulatory proteins including p53, p27, FOXO1, IkB, cyclin B1, cyclin D1 and survivin (38). XPO1 is overexpressed and associated with poor prognosis in multiple cancers including hematological malignancies and difficult to treat cancers such as pancreatic cancer and HCC (41,43,47). Inhibition of XPO1 is gaining traction as a cancer therapeutic target following clinical trials, and our data suggest it could also be a target for KIR2DS2based NK cell therapeutics (40).…”

“…NAPLVHATL, which was identified by three independent, high-quality peptide-spectrum matches ( Figure 3B), is derived from the nuclear export protein exportin-1 (XPO1). This protein is upregulated in many hematological malignancies and solid tumors including HCC, is generally associated with a poor prognosis in cancer and has been successfully targeted in clinical trials of refractory multiple myeloma (38)(39)(40)(41)(42)(43).…”

Comprehensive analysis of the value of RAB family genes in prognosis of breast invasive carcinoma

“…In recent years, molecular biology technology and bioinformatics have been widely used in cancer research. This kind of research using public databases containing many samples provides a good way in which to identify tumor biomarkers [20,21]. Here, we systematically explored the roles of RAB family genes in BRCA, including the following characteristics: prognostic values, mRNA expression levels, relationship among expression levels and clinicopathological characteristics, genetic mutations, and gene enrichment.…”