目的:本研究的目的是探讨PIK3CB在肺腺癌(LUAD)中的表达及其预后意义,并分析其促进LUAD发展的可能分子机制。
方法:用Timer和UALCAN数据库分析了LUAD和正常组织在转录水平上PIK3CB表达的差异。然后,进行免疫组织化学染色以研究蛋白质水平的PIK3CB表达,以及PIK3CB与临床特征之间的关系。采用单因素和多因素Cox回归分析确定LUAD的独立预后危险因素。使用cBioPortal数据库分析遗传改变。使用LinkedOmics数据库估计了PIK3CB的主要共表达基因和富集途径。
结果:与正常组织相比,在LUAD中,PIK3CB在转录水平和蛋白水平均有较高的表达,分别。PIK3CB的表达与LUAD患者的预后密切相关,PIK3CB蛋白表达与淋巴结转移和病理分化有关,但与性无关,年龄,胸膜侵犯,血管浸润,肿瘤部位,肿瘤大小或临床分期。PIK3CB和肿瘤大小是LUAD患者的独立危险因素。PIK3CB的表达与AKT1、AKT2呈负相关,与AKT3无显著相关性,与ARMC8、DNAJC13、PIK3R4呈强正相关。PIK3CB及其相关基因的主要富集途径包括粘附连接和磷脂酰肌醇信号通路,ErbB信号通路,Hedgehog信号通路,和C型凝集素受体信号通路。因此,我们假设PIK3CB的表达不能通过经典的PI3K/AKT途径促进LUAD的发育.
结论:PIK3CB高表达与LUAD的发展和预后恶化有关。PIK3CB是LUAD患者的独立危险因素。因此,本研究为LUAD患者的预后评估和靶向治疗提供了可靠的参考依据。
OBJECTIVE: The aim of this study was to explore the expression and prognostic significance of
PIK3CB in lung adenocarcinoma (LUAD) and to analyse the possible molecular mechanism that promotes LUAD development.
METHODS: Differences of PIK3CB expression at transcriptional level between LUAD and normal tissues were analysed with the Timer and UALCAN databases. Then, immunohistochemical staining was performed to investigate PIK3CB expression at the protein level, and relationships between
PIK3CB and clinical characteristics were accessed. Univariate and multivariate Cox regression were performed to identify the independent prognostic risk factors for LUAD. Genetic alterations were analysed using the cBioPortal database. The main coexpressed genes and enrichment pathways of PIK3CB were estimated with the LinkedOmics database.
RESULTS: Compared with normal tissues, PIK3CB was higherly expressed in LUAD at the transcriptional level and protein level, respectively.
PIK3CB expression was closely related to prognosis of LUAD patients, and
PIK3CB protein expression was associated with lymph node metastasis and pathological differentiation, but not related to sex, age, pleural invasion, vascular invasion, tumour site, tumour size or clinical stage.
PIK3CB and tumour size were independent risk factors for LUAD patients. The expression of PIK3CB was negatively correlated with AKT1 and AKT2, but there was no significant correlation with AKT3, and strong positive correlations with ARMC8, DNAJC13 and PIK3R4. The main enrichment pathways of PIK3CB and related genes included adherens junctions and the phosphatidylinositol signalling pathways, ErbB signalling pathways, Hedgehog signalling pathways, and C-type lectin receptor signalling pathways. Therefore, we hypothesized that PIK3CB expression did not promote LUAD development through the classical PI3K/AKT pathway.
CONCLUSIONS: High PIK3CB expression was associated with the development of LUAD and worse prognosis.
PIK3CB was an independent risk factor for LUAD patients. Therefore, this study provides a reliable reference for the prognostic assessment and targeted therapy for LUAD patients.