Dataset Information

Iron-sulphur cluster biogenesis factor LYRM4 is a novel prognostic biomarker associated with immune infiltrates in hepatocellular carcinoma.

ABSTRACT:

Background

LYRM4 is necessary to maintain the stability and activity of the human cysteine desulfurase complex NFS1-LYRM4-ACP. The existing experimental results indicate that cancer cells rely on the high expression of NFS1. However, the role of LYRM4 in liver hepatocellular carcinoma (LIHC) remains unclear.

Methods

In this study, we combined bioinformatics analysis and clinical specimens to evaluate the mRNA, protein expression, and gene regulatory network of LYRM4 in LIHC. Furthermore, we detected the activity of several classical iron-sulphur proteins in LIHC cell lines through UV-vis spectrophotometry.

Results

The mRNA and protein levels of LYRM4 were upregulated in LIHC. Subsequent analysis revealed that the LYRM4 mRNA expression was related to various clinical stratifications, prognosis, and survival of LIHC patients. In addition, the mRNA expression of LYRM4 was significantly associated with ALT, tumour thrombus, and encapsulation of HBV-related LIHC patients. IHC results confirmed that LYRM4 was highly expressed in LIHC tissues and showed that the expression of LYRM4 protein in LIHC was significantly correlated with age and serum low-density lipoprotein (LDL) and triglyceride (TG) content. In particular, the mRNA expression of key iron- sulphur proteins POLD1 and PRIM2 was significantly overexpressed and correlated with poor prognosis in LIHC patients. Compared with hepatocytes, the activities of mitochondrial complex I and aconitate hydratase (ACO2) in LIHC cell lines were significantly increased. These results indicated that the iron-sulphur cluster (ISC) biosynthesis was significantly elevated in LIHC, leading to ISC-dependent metabolic reprogramming. Changes in the activity of ISC-dependent proteins may also occur in paracancerous tissues. Further analysis of the biological interaction and gene regulation networks of LYRM4 suggested that these genes were mainly involved in the citric acid cycle and oxidative phosphorylation. Finally, LYRM4 expression in LIHC was significantly positively correlated with the infiltrating levels of six immune cell types, and both factors were strongly associated with prognosis.

Conclusion

LYRM4 could be a novel prognostic biomarker and molecular target for LIHC therapy. In particular, the potential regulatory networks of LYRM4 overexpression in LIHC provide a scientific basis for future research on the role of the ISC assembly mechanism and LYRM4-mediated sulphur transfer routes in carcinogenesis.

SUBMITTER: Pang Y

PROVIDER: S-EPMC8419973 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

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.

Project description:Background: Hepatocellular carcinoma (HCC) is a tumor with high malignancy and poor 5-years survival rate. Excellent tumor markers are very important for early clinical diagnosis and prognosis evaluation. Previous studies have shown that CDK2AP1 (Cyclin-dependent kinase 2-associated protein 1) is involved in cell-cycle and epigenetic regulation. In the present study, we assess CDK2AP1 expression, prognostic value, immunomodulatory and possible influencing pathways in HCC. Method: The Cancer Genome Atlas (TCGA) database was used to analyse gene expression, clinicopathology and prognosis. The protein level of CDK2AP1 in HCC tissues was detected in the Human Protein Atlas (HPA) database. The immune score in HCC to CDKAP1 expression were analyzed using ESTIMATE. Furthermore, we use Tumor IMmune Estimation Resource (TIMER) database to study CDK2AP1 expression and Immune Infiltration Levels in HCC. Co-expressed genes of CDK2AP1 were predicted and elaborated by LinkedOmics. Results: In normal liver tissues, the expression of CDK2AP1 was significantly lower than tumor tissues, and was correlated with the level of clinical stage and histologic grade in HCC patients. Patients with high expression of CDK2AP1 have a poor prognosis than patients with low CDK2AP1 expression. CDK2AP1 expression level exhibits significantly positive correlations with the number of infiltrating B cells, CD4+ T cells, CD8+ T cells, Macrophages, Neutrophils, and DCs in HCC tissues. KEGG enrichment analysis showed that the related pathways affected by CDK2AP1 mainly include: Fc gamma R-mediated phagocytosis, Th1 and Th2 cell differentiation, Cell cycle, etc. Both in vitro and in vivo experiments confirmed that CDK2AP1 promotes the proliferation and metastasis in hepatocellular carcinoma. Our results highlight the role of CDK2AP1 as an important prognostic indicator and immunotherapy target for HCC patients. Conclusion: We found CDK2AP1 as a new prognostic biomarker for HCC, which could help explain changes in the biological processes and immune environment lead to liver cancer development. Therefore, CDK2AP1 is a potential new target for HCC therapy.