Dataset Information

Prognostic potential of PRPF3 in hepatocellular carcinoma.

ABSTRACT: pre-mRNA processing factor 3 (PRPF3) is an RNA binding protein in a core component of the exon junction complex. Abnormal PRPF3 expression is potentially associated with carcinogenesis. However, the biological role of PRPF3 in hepatocellular carcinoma (HCC) remains to be determined. We analyzed PRPF3 expression via multiple gene expression databases and identified its genetic alterations and functional networks using cBioPortal. Co-expressed genes with PRPF3 and its regulators were identified using LinkedOmics. The correlations between PRPF3 and cancer immune infiltrates were investigated via Tumor Immune Estimation Resource (TIMER). PRPF3 was found up-regulated with amplification in tumor tissues in multiple HCC cohorts. High PRPF3 expression was associated with poorer overall survival (OS) and disease-free survival (DFS). Functional network analysis suggested that PRPF3 regulates spliceosome, DNA replication, and cell cycle signaling via pathways involving several cancer-related kinases and E2F family. Notably, PRPF3 expression was positively correlated with infiltrating levels of CD4+ T and CD8+ T cells, macrophages, neutrophils, and dendritic cells. PRPF3 expression showed strong correlations with diverse immune marker sets in HCC. These findings suggest that PRPF3 is correlated with prognosis and immune infiltrating in HCC, laying a foundation for further study of the immune regulatory role of PRPF3 in HCC.

SUBMITTER: Liu Y

PROVIDER: S-EPMC6977647 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Prognostic potential of PRPF3 in hepatocellular carcinoma.

Liu Yinlan Y Yang Yuhan Y Luo Yan Y Wang Juan J Lu Xiangyun X Yang Zongxing Z Yang Jin J

Aging 20200111 1

pre-mRNA processing factor 3 (PRPF3) is an RNA binding protein in a core component of the exon junction complex. Abnormal PRPF3 expression is potentially associated with carcinogenesis. However, the biological role of PRPF3 in hepatocellular carcinoma (HCC) remains to be determined. We analyzed PRPF3 expression via multiple gene expression databases and identified its genetic alterations and functional networks using cBioPortal. Co-expressed genes with PRPF3 and its r ...[more]

PMID: 31926109

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Project description:BACKGROUND: Hepatocellular carcinoma (HCC) most commonly develops in patients who have a viral infection, especially in the case of hepatitis B virus (HBV), and in patients with a chronic liver disease. HCC patients with bone metastasis (BM) suffer from pain and other symptoms that significantly reduce their quality of life. Identification of patients who are at high risk for BM after undergoing potentially curative treatment for HCC remains challenging. Here, we aimed to identify HCC BM-related genes and proteins to establish prediction biomarkers. METHODS: RNA was extracted from 48 pairs of intratumoral and peritumoral formalin-fixed, paraffin-embedded tissue from HCC patients with and without BM. A cDNA-mediated annealing, selection, extension and ligation assay containing 502 cancer-related genes was used to identify novel BM-associated genes. An additional independent study with 350 HCC patients who had undergone hepatectomy was conducted to evaluate the expression of candidate genes at the protein level using immunohistochemistry on tissue microarrays (TMAs). Of the 350 patients, 273 (78.0%) were infected with HBV. RESULTS: Seven intratumoral genes and 17 peritumoral genes were overexpressed in patients with BM, whereas 15 intratumoral genes and 28 peritumoral genes were underexpressed in patients with BM. We selected the following four genes for further analysis because they were differentially expressed in the cancer gene-specific microarray and were previously reported to be associated with BM: connective tissue growth factor (CTGF), matrix metalloproteinase-1 (MMP-1), transforming growth factor ?1 (TGF-?1), and interleukin-11 (IL-11). We assessed the protein expression of these selected genes using immunohistochemistry on TMAs including 350 HCC patient specimens. We determined that expression of intratumoral CTGF, intratumoral IL-11, and peritumoral MMP-1 were independent prognostic factors for developing BM in HCC patients. Combining intratumoral CTGF and IL-11 expression was also an independent risk factor for BM development. CONCLUSIONS: Sixty-seven genes were differentially expressed in HCC patients with and without BM. High intratumoral CTGF, positive IL-11, and high peritumoral MMP-1 expression were associated with BM after hepatectomy. Intratumoral CTGF expression combined with IL-11 expression may serve as a useful predictive biomarker for HCC BM.

Project description:Background: Hepatocellular carcinoma (HCC) represents a global health challenge. Effective biomarkers are required for an early diagnosis to improve the survival rates of HCC patients. Exonuclease 1 (EXO1) plays a significant role in the DNA repair and recombination mechanisms. This study aimed to investigate the diagnostic and prognostic roles of EXO1 in HCC. Methods: We analyzed the EXO1 expression levels in various cancers including HCC from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. RNA sequencing data were analyzed using the R packages to determine differentially expressed genes (DEGs) between high- and low-EXO1 expressing HCC tissues from the TCGA-LIHC database. A Spearman's correlation analysis was performed to determine the association between EXO1 expression and immune cell infiltration, and immune checkpoint genes and TP53. MethSurv and CBioPortal databases were used to evaluate the DNA methylation changes and genetic alterations in the EXO1 gene. A logistic regression analysis was performed to determine the association between EXO1 expression and the clinicopathological characteristics of the HCC patients. The diagnostic and prognostic predictive values of EXO1 were evaluated using the Kaplan-Meier (K-M) survival curves, diagnostic receiver operating characteristic (ROC) curves, nomogram model, and Cox regression analysis. Results: EXO1 expression levels were significantly higher in the tumor tissues and serums of HCC patients compared to the corresponding controls. The DEGs associated with EXO1 were significantly enriched in the cell proliferation pathways. EXO1 expression levels significantly correlated with immune cell infiltration, immune checkpoint genes, and TP53 in the HCC tissues. The DNA methylation status in five CpG islands of the EXO1 gene was associated with the prognosis of HCC. EXO1 expression levels in the HCC tissues were associated with the tumor grades, alpha-fetoprotein (AFP) levels, and the tumor stages. Cox regression analysis showed that EXO1 was a potential independent risk factor for the overall survival (OS) and disease-specific survival (DSS) of HCC patients. ROC curve analysis showed that EXO1 expression levels accurately distinguished HCC tissues from the adjacent normal liver tissues. Conclusion: Our study demonstrated that EXO1 was a potential diagnostic and prognostic biomarker, and a promising therapeutic target in HCC.

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Prognostic potential of PRPF3 in hepatocellular carcinoma.

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Prognostic potential of PRPF3 in hepatocellular carcinoma.

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