Prognostic Biomarker DDOST and Its Correlation With Immune Infiltrates in Hepatocellular Carcinoma

Zhu, Changyu; Jiang, Xiaolei; Tong, Rongsheng; Guan, Jianmei

doi:10.3389/fgene.2021.819520

Cited by 11 publications

(13 citation statements)

References 51 publications

(50 reference statements)

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“…Some researchers have shown that patients with skin squamous cell carcinomas that express a high percentage of DDOST have a bad prognosis [16]. Additionally, studies have revealed that DDOST is a separate prognostic factor in people with liver cancer [17]. For the first time, DDOST, which has the highest degree of node among the hub genes with dramatically decreased expression and is enriched in the protein processing in the ER pathway, was linked to CLL in our study.…”

Section: Integrated Protein-protein Interaction (Ppi) Networksupporting

confidence: 53%

Integrated Bioinformatic Analysis to Evaluate Target Genes and Pathways in Chronic Lymphocytic Leukemia

Güneş

2023

Ankara Ecz. Fak. Derg.

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Objective: The most common type of leukemia, chronic lymphocytic leukemia (CLL), is characterized by progressive accumulation of monoclonal B cells with a specific immunophenotype in the blood, bone marrow, and lymphoid organ. The goal of this research was to use bioinformatic analysis to comprehend the molecular mechanisms causing CLL and to investigate potential targets for the diagnosis and therapy of CLL. Material and Method: Expression data from CLL patients with accession numbers GSE22529 and GSE26725 were downloaded from the GEO database for bioinformatic analysis. GSE22529 data was studied with samples from 41 CLL patients and 11 healthy groups, while GSE26725 data was studied with blood samples from 12 CLL patients and 5 healthy groups. GEO2R was used to find differentially expressed genes (DEGs) in CLL patient samples and healthy control samples. The DAVID program was used to perform GO and KEGG enrichment analyses on DEGs. Using the Cytoscape software, a protein-protein interaction (PPI) network was created, and hub genes associated with CLL were identified. Result and Discussion: DEGs with p 0.05 and log2FC 0, log2FC>0 were chosen after analysis with GEO2R. In the GSE22529 dataset, 942 genes had higher expression levels in CLL patients compared with controls, while the expression of 1007 genes decreased. In the GSE26725 dataset, CLL patients had lower expression levels for 916 genes compared with controls, while 939 genes showed an increase in expression. 229 DEGs with higher expression levels and 308 DEGs with lower expression levels were found in both sets of data. It has been observed that these common genes, whose expression has changed, are enriched in protein processing in the ER, Chemokine, B-cell receptor, T-cell receptor, protein export pathways. Additionally, DDOST, RPL18, RPL18A, RPL19, RPL31, GNB3, GNB4, GNG11, GNGT1, NEDD8, UBE2M RBX1, FBXO21, SKP1, KLHL9 and CAND1 were identified as the most important genes. Our study's findings demonstrated that newly discovered genes and pathways may be candidates for CLL biomarkers that can be used for both the diagnosis and drug treatment of the disease.

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Section: Integrated Protein-protein Interaction (Ppi) Networksupporting

confidence: 53%

Integrated Bioinformatic Analysis to Evaluate Target Genes and Pathways in Chronic Lymphocytic Leukemia

Güneş

2023

Ankara Ecz. Fak. Derg.

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“…A subunit of the OST complex, DDOST, plays a vital role in N-glycosylation ( 21 ). It has been shown that DDOST also plays an important role in tumors and can serve as a marker for HCC and is closely associated with the TME ( 7 ). Numerous studies on glycomics and glycoproteomics have established a strong link between glycosylation and gliomas ( 22 , 23 ).…”

Section: Discussionmentioning

confidence: 99%

“…Some researchers found that patients with skin squamous cell carcinoma with highly expressed DDOST showed a worse prognosis ( 6 ). Moreover, studies have shown that DDOST is an independent prognostic factor in patients with liver cancer, and its expression is positively correlated with the level of Th2 cell infiltration, but negatively correlated with the level of cytotoxic cell infiltration ( 7 ). However, no studies have been conducted on DDOST in gliomas.…”

Section: Introductionmentioning

confidence: 99%

DDOST Correlated with Malignancies and Immune Microenvironment in Gliomas

et al. 2022

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Among the most common types of brain tumor, gliomas are the most aggressive and have the poorest prognosis. Dolichyl-diphosphooligosaccharide protein glycosyltransferase non-catalytic subunit (DDOST) encodes a component of the oligosaccharide transferase complex and is related to the N-glycosylation of proteins. The role of DDOST in gliomas, however, is not yet known. First, we performed a pan cancer analysis of DDOST in the TCGA cohort. The expression of DDOST was compared between glioma and normal brain tissues in the GEO and Chinese Glioma Genome Atlas (CGGA) databases. In order to explore the role of DDOST in glioma, we analyze the impact of DDOST on the prognosis of glioma patients, with the CGGA 325 dataset as a test set and the CGGA 693 dataset as a validation set. Immunohistochemistry was performed on tissue microarrays to examine whether DDOST has an impact on glioma patient survival. Next, using single-cell sequencing analysis, GSEA, immune infiltration analysis, and mutation analysis, we explored how DDOST affected the glioma tumor microenvironment. Finally, we evaluated the clinical significance of DDOST for glioma treatment by constructing nomograms and decision curve analysis (DCA) curves. We found that DDOST was overexpressed in patients with high grade, IDH wild type, 1p19q non-codel and MGMT un-methylated, which was associated with poor prognosis. Patients with high levels of DDOST, regardless of their clinical characteristics, had a worse prognosis. Immunohistochemical analysis confirmed the results of the above bioinformatics analysis. Mechanistic analysis revealed that DDOST was closely associated with the glioma microenvironment and negatively related to tumor-infiltrating B cells and CD4+ T cells and positively related to CAFs and tumor-associated macrophages. In conclusion, these findings suggested that DDOST mediated the immunosuppressive microenvironment of gliomas and could be an important biomarker in diagnosing and treating gliomas.

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“…Previous studies have shown that skewing of the Th1/Th2 cell ratio toward Th2 cells may be associated with HCC metastasis. 38 Further, Th2 cells can induce the polarization of M1 into M2 macrophages, which ultimately leads to suppression of the host immune system, thus promoting cancer development. 39 There is also evidence that energy metabolism between Th2 cells and the tumor microenvironment is interdependent, and can influence tumor development.…”

Section: Discussionmentioning

confidence: 99%

CENPO is Associated with Immune Cell Infiltration and is a Potential Diagnostic and Prognostic Marker for Hepatocellular Carcinoma

He¹,

Xie²,

Li³

et al. 2022

IJGM

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Purpose To examine the expression, clinical significance, and potential regulatory mechanism of centromere protein O (CENPO) in hepatocellular carcinoma (HCC). Methods CENPO expression in pan-cancer was studied using the TCGA-GTEx database, in HCC and normal liver tissues using the GEO and TCGA databases, and in clinical HCC samples by RT-qPCR. The diagnostic value of CENPO was assessed using receiver operating characteristic curves. Univariate and multivariate regression analyses of factors associated with HCC prognosis were performed. CENPO function and its mechanism in HCC were explored using GO, KEGG, and GSEA analyses of differentially expressed genes (DEGs). Association of CENPO expression with immune cell infiltration and immune checkpoint-associated molecules was conducted using TCGA data and the TIMER2.0 database. Relationships between CENPO expression and DNA methylation were analyzed using the UALCAN and cBioPortal databases. CENPO expression in HCC cell lines was detected using RT-qPCR. Results CENPO is upregulated in most cancers, including HCC and cell lines, and is a potential biomarker for HCC diagnosis (AUC = 0.936, 95% CI: 0.911–0.960). Higher CENPO expression was associated with poorer outcomes in patients with HCC (OS, p = 0.004; DSS, p = 0.002; PFI, p < 0.001), and CENPO was an independent predictor of factors influencing overall survival in HCC. DEGs between samples with high and low CENPO levels were enriched in various biological processes, including activation of the G2M checkpoint and other signaling pathways, while CENPO expression correlated with HCC immune cell infiltration and immune checkpoint-associated molecules, as well as CENPO promoter methylation (p < 0.001). Conclusion In HCC and cell lines, CENPO is overexpressed, a potential diagnostic marker and an indicator of poor prognosis. CENPO may regulate HCC development by influencing nuclear division and tumor immune infiltration and is regulated by methylation, making it a potential target for HCC immunotherapy.

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Prognostic Biomarker DDOST and Its Correlation With Immune Infiltrates in Hepatocellular Carcinoma

Cited by 11 publications

References 51 publications

Integrated Bioinformatic Analysis to Evaluate Target Genes and Pathways in Chronic Lymphocytic Leukemia

Integrated Bioinformatic Analysis to Evaluate Target Genes and Pathways in Chronic Lymphocytic Leukemia

DDOST Correlated with Malignancies and Immune Microenvironment in Gliomas

CENPO is Associated with Immune Cell Infiltration and is a Potential Diagnostic and Prognostic Marker for Hepatocellular Carcinoma

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