■蛋白酶体是调节蛋白质命运和消除错误折叠蛋白质的关键机制,在细胞过程中发挥重要作用。在肺癌的背景下,蛋白酶体的调节功能与疾病的病理生理密切相关,揭示细胞内的多个连接。因此,研究蛋白酶体抑制剂作为确定癌变和转移进程中潜在途径的一种手段,对于深入了解其分子机制和发现新的治疗靶点以改善其治疗至关重要。并为患者分层建立有效的生物标志物,预测性诊断,预后评估,在预测的框架内个性化治疗肺鳞癌,预防性,和个性化医疗(PPPM;3P医学)。
■这项研究鉴定了肺鳞癌(LUSC)中差异表达的蛋白酶体基因(DEPGs),并开发了通过Kaplan-Meier分析和ROC曲线验证的基因签名。该研究使用WGCNA分析来鉴定蛋白酶体共表达基因模块及其与免疫系统的相互作用。NMF分析根据蛋白酶体基因表达模式描绘了不同的LUSC亚型,而ssGSEA分析量化了LUSC样本中的免疫基因集丰度并对免疫亚型进行了分类。此外,这项研究检查了临床病理特征之间的相关性,免疫检查点,免疫评分,免疫细胞组成,以及不同风险评分组的突变状态,NMF集群,和免疫簇。
■这项研究利用DEPGs开发了LUSC的11个蛋白酶体基因签名预后模型,将样本分为高危组和低危组,总生存期差异显著。NMF分析确定了与总生存期相关的六个不同的LUSC簇。此外,ssGSEA分析基于具有临床相关性的免疫细胞浸润的丰度将LUSC样品分为四种免疫亚型。在高风险和低风险评分组之间总共确定了145个DEGs,具有显著的生物学效应。此外,发现PSMD11通过依赖于泛素-蛋白酶体系统的降解来促进LUSC进展。
■泛素化蛋白酶体基因可有效开发LUSC患者的预后模型。该研究强调了蛋白酶体在LUSC过程中的关键作用,如药物敏感性,免疫微环境,和突变状态。这些数据将有助于个性化3P医疗方法的LUSC患者的临床相关分层。Further,我们还推荐泛素化蛋白酶体系统在多水平诊断中的应用,包括多组学,液体活检,慢性炎症和转移性疾病的预测和靶向预防,和线粒体健康相关的生物标志物,LUSC3PM练习。
■在线版本包含补充材料,可在10.1007/s13167-024-00352-w获得。
UNASSIGNED: The proteasome is a crucial mechanism that regulates protein fate and eliminates misfolded proteins, playing a significant role in cellular processes. In the context of lung cancer, the proteasome\'s regulatory function is closely associated with the disease\'s pathophysiology, revealing multiple connections within the cell. Therefore, studying proteasome inhibitors as a means to identify potential pathways in carcinogenesis and metastatic progression is crucial in in-depth insight into its molecular mechanism and discovery of new therapeutic target to improve its therapy, and establishing effective biomarkers for patient stratification, predictive diagnosis, prognostic assessment, and personalized treatment for lung squamous carcinoma in the framework of predictive, preventive, and personalized medicine (PPPM; 3P medicine).
UNASSIGNED: This study identified differentially expressed proteasome genes (DEPGs) in lung squamous carcinoma (LUSC) and developed a gene signature validated through Kaplan-Meier analysis and ROC curves. The study used WGCNA analysis to identify proteasome co-expression gene modules and their interactions with the immune system. NMF analysis delineated distinct LUSC subtypes based on proteasome gene expression patterns, while ssGSEA analysis quantified immune gene-set abundance and classified immune subtypes within LUSC samples. Furthermore, the study examined correlations between clinicopathological attributes, immune checkpoints, immune scores, immune cell composition, and mutation status across different risk score groups, NMF clusters, and immunity clusters.
UNASSIGNED: This study utilized DEPGs to develop an eleven-proteasome gene-signature prognostic model for LUSC, which divided samples into high-risk and low-risk groups with significant overall survival differences. NMF analysis identified six distinct LUSC clusters associated with overall survival. Additionally, ssGSEA analysis classified LUSC samples into four immune subtypes based on the abundance of immune cell infiltration with clinical relevance. A total of 145 DEGs were identified between high-risk and low-risk score groups, which had significant biological effects. Moreover, PSMD11 was found to promote LUSC progression by depending on the ubiquitin-proteasome system for degradation.
UNASSIGNED: Ubiquitinated proteasome genes were effective in developing a prognostic model for LUSC patients. The study emphasized the critical role of proteasomes in LUSC processes, such as drug sensitivity, immune microenvironment, and mutation status. These data will contribute to the clinically relevant stratification of LUSC patients for personalized 3P medical approach. Further, we also recommend the application of the ubiquitinated proteasome system in multi-level diagnostics including multi-omics, liquid biopsy, prediction and targeted prevention of chronic inflammation and metastatic disease, and mitochondrial health-related biomarkers, for LUSC 3PM practice.
UNASSIGNED: The online version contains supplementary material available at 10.1007/s13167-024-00352-w.