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Protein kinase C substrate 80K-H (PRKCSH) plays a crucial role in the protein N-terminal glycosylation process, with emerging evidence implicating its involvement in tumorigenesis. To comprehensively assess PRKCSH's significance across cancers, we conducted a pan-cancer analysis using data from The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), and Cancer Cell Line Encyclopedia (CCLE). We assessed aberrant PRKCSH mRNA and protein expression, examined its prognostic implications, and identified correlations with clinical features, tumor mutational burden (TMB), microsatellite instability (MSI), and tumor immunity across cancer types. We explored PRKCSH gene alterations, DNA methylation, and their impact on patient prognosis. Gene Set Enrichment Analysis (GSEA) and single-cell analysis revealed potential biological roles. Additionally, we investigated drug susceptibility and conducted Connectivity Map (Cmap) analysis. Key findings revealed that PRKCSH exhibited overexpression in most tumors, with a significant association with poor overall survival (OS) in six cancer types. Notably, PRKCSH expression demonstrated variations across disease stages, primarily increasing in advanced stages among eleven tumor types. Moreover, PRKCSH exhibited significant correlations with TMB in five cancer categories, MSI in eight, and displayed associations with immune cell populations in pan-cancer analysis. Genetic variations in PRKCSH were identified across 26 tumor types, suggesting favorable disease-free survival. Furthermore, PRKCSH methylation displayed a significant negative correlation with its expression in 27 tumor types, with a marked decrease compared to normal tissues in ten tumors. Cmap predicted 24 potential therapeutic small molecules in over four cancer types. This study highlights that PRKCSH, as a potential oncogene, may be a promising prognostic marker and therapeutic target of immunotherapy for a range of malignancies. [ABSTRACT FROM AUTHOR]

Glioma is the most common primary malignant tumor in the central nervous system. Disulfidptosis is a recently identified programmed cell death in tumor cells overexpressing SLC7A11 under glucose starvation. Clinical prognostic significance of disulfidptosis has been reported in several tumors, and in this study, we explored the correlation of disulfidptosis with clinical prognosis, immune cell infiltration, and immunotherapy response in glioma. A total of 1592 glioma patients were included in this study, including 691 glioma patients from The Cancer Genomic Atlas (TCGA), 300 patients with from the Chinese Glioma Genomic Atlas (CGGA) array, 325 patients from CGGA sequencing, and 276 patients from Gene Expression Omnibus (GEO) GSE16011. R software (V4.2.2) and several R packages were applied to develop the risk score model and correlation calculation and visualization. Three disulfidptosis-related genes, LRPPRC, RPN1, and GYS1, were screened out and applied to establish the risk score model. Low-risk patients exhibit favorable prognosis, and the disulfidptosis-related signature significantly correlated with clinicopathological properties, molecular subtypes, and immunosuppressive microenvironment of glioma patients. We developed a disulfidptosis-related risk model to predict the prognosis and immune features in glioma patients, and this risk model may be applied as an independent prognostic factor for glioma. [ABSTRACT FROM AUTHOR]

Methyltransferase-like protein 7A (METTL7A) is an m6A RNA methyltransferase that has been linked to cancer prognosis and drug resistance. However, a comprehensive analysis of METTL7A is lacking. The expression of METTL7A, prognostic performance, correlation with microsatellite instability (MSI), tumor mutational burden (TMB), and immune infiltration was investigated in The Cancer Genome Atlas (TCGA). Immunohistochemistry staining was applied to detect METTL7A in 6 tumors. METTL7A was significantly decreased in 19 cancers in TCGA including LUAD. Alterations of METTL7A include amplification and mutation, and epigenetic alterations revealed increased promoter methylation may result in down-regulation of METTL7A in LUAD. We also found that METTL7A was linked to both TMB and MSI in LUAD. METTL7A was increasingly correlated with invasive immune cells, while being negatively associated with Macrophages M0, Mast cells activated, activated memory CD4 T cells, CD8 T cells, and follicular helper T cells in several tumors. Additionally, METTL7A showed similar correlation with immune therapy-related genes across cancers. Our biological validation found that the protein levels of METTL7A were down-regulated in breast cancer (BRCA), endometrioid cancer (UCEC), colon cancer (COAD), prostate cancer (PRAD), and kidney clear cell carcinoma (KIRC), as detected by immunohistochemistry staining. Overall, our work indicates that METTL7A may serve as promising diagnostic and prognostic indicator of LUAD, and our work sheds light on the potential immunological and prognostic roles of METTL7A in human cancers. [ABSTRACT FROM AUTHOR]

Waardenburg syndrome type 4 (WS4) or Waardenburg-Shah syndrome is a rare genetic disorder with a prevalence of <1/1,000,000 and characterized by the association of congenital sensorineural hearing loss, pigmentary abnormalities, and intestinal aganglionosis. There are three types of WS4 (WS4A-C) caused by mutations in endothelin receptor type B, endothelin 3, and SRY-box 10 (SOX10), respectively. This study investigated a genetic mutation in a Chinese family with one WS4 patient in order to improve genetic counselling. Genomic DNA was extracted, and mutation analysis of the three WS4 related genes was performed using Sanger sequencing. We detected a de novo heterozygous deletion mutation [c.1333delT (p.Ser445Glnfs*57)] in SOX10 in the patient; however, this mutation was absent in the unaffected parents and 40 ethnicity matched healthy controls. Subsequent phylogenetic analysis and three-dimensional modelling of the SOX10 protein confirmed that the c.1333delT heterozygous mutation was pathogenic, indicating that this mutation might constitute a candidate disease-causing mutation. [ABSTRACT FROM AUTHOR]

Recent studies investigating the association of the Ras-like without CAAX 2 (RIT2) polymorphism, rs12456492, with Parkinson's disease (PD) are controversial. We performed a meta-analysis to study the association between rs12456492 and PD susceptibility in Asian populations. Literature searches of PubMed and Embase were performed up to June 3, 2015, and the strength of the association between rs12456492 and PD was evaluated by odds ratios (OR) and 95% confidence intervals (CI). Four studies conducted between 2013 and 2015, comprising 2017 PD cases and 2010 controls, were included in the meta-analysis. Significant association of rs12456492 with PD was found in the dominant (GG + AG vs. AA: OR = 1.26, 95% CI = 1.20-1.44, P = 0.00) and additive models (GG vs. AA: OR = 1.38, 95% CI = 1.03-1.83, P = 0.030). Although sensitivity analysis found that the overall result was stable only in the dominant genetic model, a publication bias was also detected. Therefore, the results should be treated with caution. The current meta-analysis suggested that rs12456492 might be associated with increased PD risk in Asian populations, but studies using larger sample sizes and different ethnic populations will be needed to further confirm this association. [ABSTRACT FROM AUTHOR]