Pan-cancer analysis of the prognostic and immunological role of PSMB8

Chen, Danxiang; Jin, Cong; Dong, Xubin; Wen, Jialiang; Xia, Erjie; Wang, Qingxuan; Wang, Ouchen

doi:10.1038/s41598-021-99724-9

Cited by 17 publications

(19 citation statements)

References 22 publications

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“…: PSMB8, NFKB1, ALB, EDN1 , and ESR1 . Proteasome subunit beta 8) is a catalytic subunit involved in tumor infiltration and neuroinflammation ( 21 , 22 ). Nuclear factor kappa B1 is a classic transcriptional regulator with multi-system involvement ( 23 ).…”

Section: Discussionmentioning

confidence: 99%

Integrated bioinformatic analysis reveals immune molecular markers and potential drugs for diabetic cardiomyopathy

et al. 2022

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Diabetic cardiomyopathy (DCM) is a pathophysiological condition induced by diabetes mellitus that often causes heart failure (HF). However, their mechanistic relationships remain unclear. This study aimed to identify immune gene signatures and molecular mechanisms of DCM. Microarray data from the Gene Expression Omnibus (GEO) database from patients with DCM were subjected to weighted gene co-expression network analysis (WGCNA) identify co-expression modules. Core expression modules were intersected with the immune gene database. We analyzed and mapped protein-protein interaction (PPI) networks using the STRING database and MCODE and filtering out 17 hub genes using cytoHubba software. Finally, potential transcriptional regulatory factors and therapeutic drugs were identified and molecular docking between gene targets and small molecules was performed. We identified five potential immune biomarkers: proteosome subunit beta type-8 (PSMB8), nuclear factor kappa B1 (NFKB1), albumin (ALB), endothelin 1 (EDN1), and estrogen receptor 1 (ESR1). Their expression levels in animal models were consistent with the changes observed in the datasets. EDN1 showed significant differences in expression in both the dataset and the validation model by real-time quantitative PCR (qPCR) and Western blotting(WB). Subsequently, we confirmed that the potential transcription factors upstream of EDN1 were PRDM5 and KLF4, as its expression was positively correlated with the expression of the two transcription factors. To repurpose known therapeutic drugs, a connectivity map (CMap) database was retrieved, and nine candidate compounds were identified. Finally, molecular docking simulations of the proteins encoded by the five genes with small-molecule drugs were performed. Our data suggest that EDN1 may play a key role in the development of DCM and is a potential DCM biomarker.

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Section: Discussionmentioning

confidence: 99%

Integrated bioinformatic analysis reveals immune molecular markers and potential drugs for diabetic cardiomyopathy

et al. 2022

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“…As the member of immunoproteasome, LMP7 participated in the antigen presentation, cell cycle regulation, and cell signal transduction (18)(19)(20). At present, many studies show that abnormal expression of PSMB8 correlates with multiple cancers, including BC (21)(22)(23)(24)(25). However, the results obtained from different studies are not the same.…”

Section: Discussionmentioning

confidence: 99%

Methylation of Immune-Related Genes in Peripheral Blood Leukocytes and Breast Cancer

Tian

et al. 2022

Front. Oncol.

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Abnormal DNA methylation contributes to breast cancer (BC). Immune-related genes play crucial roles in BC development and progression. This study aims to investigate the effect of methylation of immune-related genes in peripheral blood leukocytes (PBLs) on BC risk. GSE51032 and GSE104942 datasets were used to identify significantly differentially methylated CpG sites (DMCs) of immune-related genes. A case-control study was conducted using MethylTarget sequencing to validate the relationship between the methylation levels of the screened genes and BC risk. We also evaluated the association between methylation haplotypes of screened genes and BC risk. Moreover, we sorted the blood leukocytes into T cells, B cells, and monocytes to detect the difference of DNA methylation in different cell subtypes. A total of five DMCs were screened from GEO datasets, including cg01760846 (PSMC1), cg07141527 (SPPL3), cg15658543 (CARD11), cg21568368 (PSMB8), and cg24045276 (NCF2). In the case-control study, there were significant associations between methylation of the CpG sites in the five genes and BC risk. Methylation haplotype burdens of PSMC1, CARD11, and PSMB8 were associated with reduced BC risk. Moreover, there were heterogeneities in the methylation levels of the genes in different cell subtypes. In conclusion, methylation of PSMC1, SPPL3, CARD11, PSMB8, and NCF2 in PBLs were associated with BC risk. The five-gene methylation could be the potential biomarkers for predicting BC risk.

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“…Molecular subtype of breast cancer was determined after assessing the receptor status [expression of ER and PR], HER-2 status and proliferative activity (Ki67 expression) in biopsy and surgical specimens using the According to the American Society of Clinical Oncology/ College of American Pathologists (ASCO/CAP) guidelines, ER and PR expression was considered positive when nuclear immunoreactivity was ≥1% of tumor cells (42). HER-2positive protein status was defined as a score of 3+ or 2+ by IHC along with confirmed amplification of the c-erbB2 gene using fluorescence in situ hybridization (FISH).…”

Section: Ihcmentioning

confidence: 99%

“…Using various databases and platforms (Oncomine, cBioPortal and Cytoscaped and METABRIC, TCGA, CCLE Project and STRING), numerous published studies demonstrated the prognostic value of the gene expressions of various proteasome subunits both in breast cancer and in other cancers in terms of long-term overall and longterm progression-free survivals. In particular, the authors reported on the prognostic significance of the expression of the PSMC family genes encoding subunits of the 19S regulatory complex of the proteasomes, the expression of the PSMA family genes encoding the α subunits of the proteasome nucleus, and the expression of the PSMB8 gene responsible for the formation of the immune LMP7 subunit (40)(41)(42). Almost all databases concern the expression of genes encoding various subunits of the proteasome complex.…”

Section: Introductionmentioning

confidence: 99%

Five-year survival in luminal breast cancer patients: relation with intratumoral activity of proteasomes

Шашова¹,

Kolegova²,

Какурина³

et al. 2022

Transl Breast Cancer Res

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Background: The purpose of the study was to analyze the relationship between the caspase-like (CL) and chymotrypsin-like (ChTL) activities of proteasomes and the 5-year overall and metastasis-free survival rates in patients with luminal breast cancer. Methods:The study included 117 patients with primary operable invasive breast cancer (T 1-2 N 0-1 M 0 ). Tissue samples from breast cancer patients were obtained as a result of the radical mastectomy or breast conserving surgery, which was a first line of therapy. The ChTL and CL proteasomes activities in the tumor tissue and in the surrounding adjacent breast tissues were assessed using the fluorometric method. The coefficients of ChTL (cChTL) and CL (cCL) proteasomes activities were also determined. The coefficients were calculated as the ratio of the corresponding proteasomes activity in the tumor tissue to the surrounding adjacent breast tissues. Within 5 years of follow-up, hematogenous metastases occurred in 14% of patients with luminal A breast cancer, in 31% of patients with luminal B human epidermal growth factor receptor-2 (HER-2) negative and in 23% of patients with luminal B HER-2 positive breast cancers. The study protocol was approved by the Local Ethics Committee of the Cancer Research Institute of Tomsk National Research Medical Center. Written informed consent was obtained from all patients.Results: An increase in the ChTL and CL proteasomes activities was shown in all studied molecular subtypes of breast cancer compared to adjacent tissues. It was found that the cChTL of >35.9 U/mg protein and the cCL of >2.21 in breast cancer patients were associated with the development of distant metastases.In patients with luminal A breast cancer, the 5-year metastasis-free survival rates were associated only with the value of cCL of proteasomes (log-rank test: P=0.008). In patients with luminal B HER-2 negative breast cancer, the 5-year metastasis-free survival rates were associated with the levels of ChTL and cCL proteasomes activities (log-rank test: P=0.02 and P=0.04, respectively). Conclusions:The data obtained on the correlation of 5-year metastasis-free survival rates with the level of

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Pan-cancer analysis of the prognostic and immunological role of PSMB8

Cited by 17 publications

References 22 publications

Integrated bioinformatic analysis reveals immune molecular markers and potential drugs for diabetic cardiomyopathy

Integrated bioinformatic analysis reveals immune molecular markers and potential drugs for diabetic cardiomyopathy

Methylation of Immune-Related Genes in Peripheral Blood Leukocytes and Breast Cancer

Five-year survival in luminal breast cancer patients: relation with intratumoral activity of proteasomes

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