Multi-omics analysis of DNA replication-associated primase polymerase (PRIMPOL) in pan-cancer: A potential target for prognosis and immune response

Background: It is critical to understand the mechanisms of human cancers in order to develop the effective anti-cancer therapeutic strategies. Recent studies indicated that primase polymerase (PRIMPOL) is strongly associated with the development of human cancers. Nevertheless, a systematic pan-cancer analysis of PRIMPOL remains to be further clarified. Method: Comprehensive multi-omics bioinformatics algorithms, such as TIMER2.0, GEPIA2.0 and cBioPortal, were utilized to evaluate the biological roles of PRIMPOL in pan-cancer, including the expression profiles, genomic alterations, prognostic values and immune regulation. Results: PRIMPOL was upregulated in glioblastoma multiforme and kidney renal clear cell carcinoma. The brain lower grade glioma patients with enhanced PRIMPOL expression displayed poor prognostic values. We also demonstrated the PRIMPOL's immunomodulating effects on pan-cancer as well as its genomic changes and methylation levels. The aberrant expression of PRIMPOL was linked to various cancer-associated pathways, including DNA damage response, DNA repair, and angiogenesis, according to single-cell sequencing and function enrichment. Conclusions: This pan-cancer analysis offers a thorough review of the functional roles of PRIMPOL in human cancers, suggesting PRIMPOL as a potentially important biomarker for the progression and immunotherapy of various cancers.</p

The Association between E326K of GBA and the Risk of Parkinson’s Disease

It is reported that both the homozygous and heterozygous states of GBA mutations which are the causes of Gaucher disease (GD) are linked to the risk of PD. However, the GBA variant p.E326K (c.1093G > A, rs2230288), which does not result in GD in homozygous carriers, has triggered debate among experts studying Parkinson's disease (PD). In order to determine if the E326K variant of GBA is associated with the risk of PD, a standard meta-analysis was conducted by searching and screening publications, data extraction, and statistical analysis. Finally, a total of 15 publications, containing 5,908 PD patients and 5,605 controls, were included in this analysis. The pooled OR of the E326K genotype analysis was 1.99 (95% CI: 1.57–2.51). The minor allele frequencies of E326K for PD patients and controls were 1.67% and 1.03%, respectively. The pooled OR for the minor allele A was 1.99 (95% CI: 1.58–2.50). According to the subgroup analysis, we found that the significant differences between PD patients and controls for both genotype and allele of E326K also exist in Asians and Caucasians, respectively. In this study, we found that E326K of GBA is associated with the risk of PD in total populations, Asians, and Caucasians, respectively. Further studies are needed to clarify the role of GBA in the pathogenesis of PD

High expression of six-transmembrane epithelial antigen of prostate 3 promotes the migration and invasion and predicts unfavorable prognosis in glioma

Recent studies have suggested that ferroptosis, a form of iron-dependent regulated cell death, might play essential roles in tumor initiation and progression. Six-transmembrane epithelial antigen of prostate 3 (STEAP3) is a ferrireductase involved in the regulation of intracellular iron homeostasis. However, the clinical significance and biological function of STEAP3 in human cancers remain poorly understood. Through a comprehensive bioinformatics analysis, we found that STEAP3 mRNA and protein expression were up-regulated in GBM, LUAD, and UCEC, and down-regulated in LIHC. Survival analysis indicated that STEAP3 had prognostic significance only in glioma. Multivariate Cox regression analysis revealed that high STEPA3 expression was correlated with poor prognosis. STEAP3 expression was significantly negatively correlated with promoter methylation level, and patients with lower STEAP3 methylation level had worse prognosis than those with higher STEAP3 methylation level. Single-cell functional state atlas showed that STEAP3 regulated epithelial-to-mesenchymal transition (EMT) in GBM. Furthermore, the results of wound healing and transwell invasion assays demonstrated that knocking down STEAP3 inhibited the migration and invasion of T98G and U251 cells. Functional enrichment analysis suggested that genes co-expressed with STEAP3 mainly participated in inflammation and immune-related pathways. Immunological analysis revealed that STEAP3 expression was significantly correlated with immune infiltration cells, including macrophages and neutrophils, especially the M2 macrophages. Individuals with low STEAP3 expression were more likely to respond to immunotherapy than those with high STEAP3 expression. These results suggest that STEAP3 promotes glioma progression and highlight its pivotal role in regulating immune microenvironment