Dataset Information

Prognostic Significance of Pregnancy Zone Protein and Its Correlation with Immune Infiltrates in Hepatocellular Carcinoma.

ABSTRACT: Aim:Human pregnancy zone protein (PZP) is a pregnancy-related protein which is increased dramatically during pregnancy. However, the expression of PZP and its prognostic value, association with tumor-infiltrating immune cells (TIICs) in microenvironment and potential biological process in HCC were unclear. Methods:The PZP expression, clinicopathology analysis and its influence on survival were analyzed by GEPIA and HPA. Fifty-nine HCC samples and 30 corresponding noncancerous tissues were collected and retrospectively analyzed to verify the results of bioinformatics analysis. Further, TIMER and CIBERSORT were performed to identify the significantly alerted biological process and affections of PZP expression on the immune system in patients with HCC. Finally, IHC assay of CD4+ T cells and Treg cells was performed to confirm the results of immune infiltrates analysis by TIMER and CIBERSORT. Results:PZP expression was downregulated in HCC tissues and its low level was substantially correlated with poor prognosis in patients with HCC. TIMER analysis showed that PZP expression had a positive correlation with the levels of macrophage and neutrophil. Furthermore, CIBERSORT analysis showed that resting memory CD4 T cells were increased in high PZP expression group, while the results of Tregs were the opposite. Finally, the IHC results of CD4+ T cells and Treg cells showed that only Tregs were negatively associated with PZP expression. Conclusion:PZP was identified as a novel prognosis biomarker of HCC and might play a vital role in the regulation and recruitment of TIICs in HCC immune microenvironment.

SUBMITTER: Su L

PROVIDER: S-EPMC7553665 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Prognostic Significance of Pregnancy Zone Protein and Its Correlation with Immune Infiltrates in Hepatocellular Carcinoma.

Su Lisa L Zhang Genhao G Kong Xiangdong X

Cancer management and research 20201009

<h4>Aim</h4>Human pregnancy zone protein (PZP) is a pregnancy-related protein which is increased dramatically during pregnancy. However, the expression of PZP and its prognostic value, association with tumor-infiltrating immune cells (TIICs) in microenvironment and potential biological process in HCC were unclear.<h4>Methods</h4>The PZP expression, clinicopathology analysis and its influence on survival were analyzed by GEPIA and HPA. Fifty-nine HCC samples and 30 corresponding noncancerous tiss ...[more]

PMID: 33116846

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Project description:BackgroundSeveral markers have been reported to be specific for hepatic cancer stem cells (HCSCs), which is usually thought to be highly associated with poor clinical outcomes. Tumor-infiltrating immune cells act as an important factor for oncogenesis. Little is known about the correlation of HCSC markers to prognosis and immune infiltrates.MethodsExpression of HCSC markers was analyzed through Oncomine database, Gene Expression Profiling Interactive Analysis (GEPIA) and Integrative Molecular Database of Hepatocellular Carcinoma (HCCDB), respectively. The prognostic effect of HCSC markers was evaluated using Kaplan-Meier plotter in association with different tumor stages, risk factors, and gender. The correlation of HCSC markers to tumor-infiltrating immune cells was tested by Tumor Immune Estimation Resource (TIMER). HCSC markers related gene sets were investigated by GEPIA, with their biological functions being analyzed by Cytoscape software.ResultsThe expression level of 10 HCSC markers in HCC was higher than that in normal tissues in at least one database. Among them, high expression of CD24, SOX9, and SOX12 was positively correlated with poor prognosis (CD24: OS P = 0.0012, PFS P = 7.9E-05. SOX9: OS P = 0.012. SOX12: OS P = 0.0004, PFS P = 0.0013, respectively). However, the expression of CD13, CD34 and ALDH1A1 was associated with prolonged OS and PFS. SOX12 was significantly upregulated in poor prognosis of HCC patients with different conditions. Besides, total nine HCSC markers were identified to be positively associated with immune infiltration, including SOX12. Furthermore, Toll-like receptor signaling pathway was found to be one major pathway of these HCSC markers related gene networks.ConclusionOur results suggest that seven upregulated HCSC markers (CD90, EpCAM, CD133, CD24, SOX9, CK19, and SOX12) are related with poor prognosis and immune infiltration in HCC. In addition, we find that high SOX12 expression remarkably affect prognosis in male HCC patients but not in female. HCC patients under viral infection or alcohol intake with increased SOX12 expression had poorer prognosis. Therefore, HCSCs markers likely play an important role in tumor related immune infiltration and SOX12 might be a potential therapeutic target in patients with HCC.

Project description:BackgroundHepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide. Recently, competing endogenous RNAs (ceRNA) have revealed a significant role in the progression of HCC. Herein, we aimed to construct a ceRNA network to identify potential biomarkers and illustrate its correlation with immune infiltration in HCC.MethodsRNA sequencing data and clinical traits of HCC patients were downloaded from TCGA. The limma R package was used to identify differentially expressed (DE) RNAs. The predicted prognostic model was established using univariate and multivariate Cox regression. A K-M curve, TISIDB and GEPIA website were utilized for survival analysis. Functional annotation was determined using Enrichr and Reactome. Protein-to-protein network analysis was implemented using SRTNG and Cytoscape. Hub gene expression was validated by quantitative polymerase chain reaction, Oncomine and the Hunan Protein Atlas database. Immune infiltration was analyzed by TIMMER, and Drugbank was exploited to identify bioactive compounds.ResultsThe predicted model that was established revealed significant efficacy with 3- and 5-years of the area under ROC at 0.804 and 0.744, respectively. Eleven DEmiRNAs were screened out by a K-M survival analysis. Then, we constructed a ceRNA network, including 56 DElncRNAs, 6 DEmiRNAs, and 28 DEmRNAs. The 28 DEmRNAs were enriched in cancer-related pathways, for example, the TNF signaling pathway. Moreover, six hub genes, CEP55, DEPDC1, KIF23, CLSPN, MYBL2, and RACGAP1, were all overexpressed in HCC tissues and independently correlated with survival rate. Furthermore, expression of hub genes was related to immune cell infiltration in HCC, including B cells, CD8+ T cells, CD4+ T cells, monocytes, macrophages, neutrophils, and dendritic cells.ConclusionThe findings from this study demonstrate that CEP55, DEPDC1, KIF23, CLSPN, MYBL2, and RACGAP1 are closely associated with prognosis and immune infiltration, representing potential therapeutic targets or prognostic biomarkers in HCC.

Project description:BackgroundEpigenetic alterations contribute greatly to metastasis and dissemination in hepatocellular carcinoma (HCC). SMARCC1, as a SWI/SNF chromatin remodeling factor, has been reported to play important roles in many cancers. For the first time, with the bioinformatics analysis and wet-bench experiments, we explored the biological significance of SMARCC1 and its potential as putative therapeutic target in HCC.MethodsThe mRNA expression profiles and prognostic value of SMARCC1 were analyzed in the Oncomine, UALCAN and Kaplan-Meier Plotter databases. The expression of SMARCC1 and associated clinicopathological factors were further evaluated using a tissue microarray. Differentially expressed genes associated with SMARCC1 in HCC were obtained and analyzed via the LinkedOmics and GEPIA databases and Cytoscape software. To verify the important role of SMARCC1 in HCC, we knocked down and overexpressed SMARCC1 in different hepatic cell lines and conducted several functional experiments. Then, we evaluated the mutation profiles and transcriptional regulators of SMARCC1 using the cBioPortal, COSMIC, CistromeDB and TCGA databases. Finally, we addressed the relationship of SMARCC1 expression with immune cell infiltration via TIMER database analysis.ResultsThrough data mining and tissue microarray verification, we found that the protein and mRNA levels of SMARCC1 are high in tumor tissues, which has remarkable diagnostic value in HCC patients. SMARCC1 and its hub genes showed prognostic value in HCC. Furthermore, we confirmed that SMARCC1 influenced the proliferation, migration, and invasion of HCC cells. Moreover, correlation analyses revealed that SMARCC1 expression was positively correlated with ZBTB40 transcription factors and negatively correlated with the DNA methylation level. Overall, we found that SMARCC1 affects immune infiltration and plays a tumor-promoting role in HCC.ConclusionsSMARCC1 is overexpressed and is a putative prognostic predictor in HCC. Due to the tumor-promoting role of SMARCC1, treatments inhibiting DNA methyltransferases and transcription factors or weakening the role of SMARCC1 in immune infiltration might improve the survival of HCC patients.

Dataset Information

Prognostic Significance of Pregnancy Zone Protein and Its Correlation with Immune Infiltrates in Hepatocellular Carcinoma.

Publications

Prognostic Significance of Pregnancy Zone Protein and Its Correlation with Immune Infiltrates in Hepatocellular Carcinoma.

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