Dataset Information

Hydroxysteroid 17-Beta Dehydrogenase 6 Is a Prognostic Biomarker and Correlates with Immune Infiltrates in Hepatocellular Carcinoma.

ABSTRACT:

Background

Hepatocellular carcinoma (HCC) is a common malignancy worldwide with poor outcomes. Therefore, it is important to identify a valuable prognostic biomarker for HCC. The present study aimed to identify novel prognostic biomarkers for HCC and evaluate the potential role of hub genes in HCC.

Methods

Weighted gene co-expression network analysis and protein-protein interaction analysis were performed to identify important potential prognostic genes. The expression of hub genes was confirmed by the GEPIA, Oncomine, UALCAN, and HPA database. Furthermore, survival analysis of hub genes was performed using the Kaplan-Meier plotter database. Finally, we investigated the association between hub genes and immune factors in HCC through GSEA, the TIMER, and TISIDB database.

Results

HSD17B6 expression was significantly lower in HCC than in normal tissues. Low HSD17B6 expression is associated with poorer overall survival and progression-free survival in HCC patients, particularly at medium disease stages (stage II and III or grade III). HSD17B6 showed a strong correlation with tumor-infiltrating B cells, CD4?+?and CD8?+?T cells, macrophages, neutrophils, and dendritic cells. Somatic copy number alteration might be the main cause of the negative correlation between HSD17B6 expression and immune infiltration. HSD17B6 expression in HCC negatively correlated with the expression of several immune cell markers, including exhausted T cell markers, PD-1 and CTLA-4, suggesting its role in regulating tumor immunity.

Conclusions

HSD17B6 is a potential prognostic biomarker that determines cancer progression and is correlated with tumor immune cells infiltration in HCC.

SUBMITTER: Wu M

PROVIDER: S-EPMC7835108 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Publications

Hydroxysteroid 17-Beta Dehydrogenase 6 Is a Prognostic Biomarker and Correlates with Immune Infiltrates in Hepatocellular Carcinoma.

Wu Min M Jiang Li L

Digestive diseases and sciences 20210126 1

<h4>Background</h4>Hepatocellular carcinoma (HCC) is a common malignancy worldwide with poor outcomes. Therefore, it is important to identify a valuable prognostic biomarker for HCC. The present study aimed to identify novel prognostic biomarkers for HCC and evaluate the potential role of hub genes in HCC.<h4>Methods</h4>Weighted gene co-expression network analysis and protein-protein interaction analysis were performed to identify important potential prognostic genes. The expression of hub gene ...[more]

PMID: 33495920

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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.

Project description:Background The prognosis is poor for hepatocellular carcinoma (HCC), a tumor and cancer associated with inflammation that is common. New data showed that significant levels of KIAA1522 were expressed in HCC tissues and cell lines, suggesting that KIAA1522 may be a highly useful prognostic marker for HCC. However, its biochemical processes and impacts on the immune system go deeper. Objective To verify the significance of KIAA1522 in HCC and investigate its related carcinogenic mechanisms. Methods Studies examining the relationship between KIAA1522 expression and clinical-pathologic characteristics in HCC have been checked in the Cancer Genome Atlas (TCGA) database. A receiver operating characteristic (ROC) curve was used to assess the diagnostic efficacy of KIAA1522 in HCC. Western blot analysis was used to find the presence of the KIAA1522 protein in the tumor and paraneoplastic tissues of eight randomly chosen HCC patients. The GSVA program in R language was used to evaluate the relationship between KIAA1522 and immune cell infiltration in HCC. We searched the Search Tool for the Retrieval of Interacting Genes (STRING) database for interacting proteins connected to the expression of KIAA1522. Pathways were involved in the enrichment analysis of KIAA1522 to anticipate potential mechanisms through which KIAA1522 may affect immunological infiltration. Results Our study found that KIAA1522 was commonly elevated in HCC tumor tissues and that it also signaled a bad outcome. We found an inverse link between KIAA1522 and cytotoxic cells and an inverse relationship between KIAA1522 and Th2 cell infiltration. In STRING analysis, the top 5 coexpressed proteins of KIAA1522 were BAIAP2, NCK2, TSNAXIP1, POGK, and KLHL31. The effect of KIAA1522 on HCC may entail cell cycle alteration, an immunological response, and suppression of the PPAR signaling pathway. Conclusion High expression of KIAA1522 was linked to HCC immune cell infiltration, disease progression, and a poor prognosis.

Dataset Information

Hydroxysteroid 17-Beta Dehydrogenase 6 Is a Prognostic Biomarker and Correlates with Immune Infiltrates in Hepatocellular Carcinoma.

Background

Methods

Results

Conclusions

Publications

Hydroxysteroid 17-Beta Dehydrogenase 6 Is a Prognostic Biomarker and Correlates with Immune Infiltrates in Hepatocellular Carcinoma.

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