PDF(Pubmed)
Abstract：
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.
摘要：
蛋白激酶C底物80K-H(PRKCSH)在蛋白质N端糖基化过程中起着至关重要的作用,有新的证据表明它参与了肿瘤发生。为了全面评估PRKCSH在癌症中的意义，我们使用癌症基因组图谱（TCGA）的数据进行了泛癌症分析，基因型-组织表达(GTEx),和癌细胞系百科全书（CCLE）。我们评估了PRKCSHmRNA和蛋白表达异常，检查了其预后影响，并确定了与临床特征的相关性，肿瘤突变负荷（TMB），微卫星不稳定性（MSI），和癌症类型的肿瘤免疫力。我们探索了PRKCSH基因改变，DNA甲基化，以及它们对患者预后的影响。基因集富集分析（GSEA）和单细胞分析揭示了潜在的生物学作用。此外,我们调查了药物敏感性并进行了连接图(Cmap)分析.主要研究结果表明，PRKCSH在大多数肿瘤中表现出过表达，与6种癌症类型的总体生存率（OS）差显著相关。值得注意的是,PRKCSH表达显示出不同疾病阶段的差异，主要在11种肿瘤类型的晚期增加。此外，PRKCSH在五个癌症类别中与TMB表现出显著相关性，八岁的MSI，并在泛癌症分析中显示与免疫细胞群体的关联。在26种肿瘤类型中发现了PRKCSH的遗传变异，表明有利的无病生存。此外，PRKCSH甲基化与其在27种肿瘤中的表达呈显著负相关,与正常组织相比，在十个肿瘤中明显减少。Cmap预测了四种癌症类型中的24种潜在治疗性小分子。这项研究强调了PRKCSH，作为一种潜在的致癌基因，可能是一系列恶性肿瘤免疫治疗的一个有希望的预后标志物和治疗靶点。
