背景:p16,p53和增殖细胞核抗原(pcna)基因在许多染色质修饰中起重要作用,并已发现在多种肿瘤组织中高表达。因此,它们已被用作一些肿瘤治疗的靶基因。然而,p16,p53和pcna基因在人肉瘤中的差异表达及其对预后的影响尚未得到广泛报道。
方法:Oncomine数据集用于分析p16,p53和pcna基因的转录水平,基因表达谱交互分析(GEPIA)数据集用于分析p16,p53和pcna的差异表达。通过Western印迹进一步分析p16、p53和pcna的表达水平。GEPIA和Kaplan-Meier分析用于分析p16,p53和pcna的预后价值。此外,使用cBioPortal数据集分析了p16,p53和pcna基因突变及其与总生存期(OS)和无病生存期(DFS)的关联。此外,使用Oncomine分析了与p16,p53和pcna共表达的基因。DAVID数据集用于分析p16,p53,pcna,并通过基因本体论(GO)和Metascape共表达基因来构建网络图。最后,肿瘤免疫评估资源(TIMER)报道了肉瘤患者p16,p53和pcna的免疫细胞浸润。
结果:p16、p53和pcna在人肉瘤组织和几乎所有肉瘤细胞系中表达上调。Western印迹显示骨肉瘤细胞系中p16,p53和pcna的表达升高。pcna的表达与OS相关,p16,p53和pcna的表达与无复发生存率相关,p16基因突变与OS和DFS呈负相关。我们还发现p16,p53和pcna基因与肉瘤中的免疫细胞浸润呈正/负相关。
结论:本研究结果表明,p16、p53和pcna可显著影响肉瘤患者的生存和免疫状态。因此,p16,p53和pcna可作为人类肉瘤预后和免疫浸润的潜在生物标志物,并为肉瘤的治疗提供可能的靶标。
BACKGROUND: p16, p53, and proliferating cell nuclear antigen (pcna) genes play significant roles in many chromatin modifications and have been found to be highly expressed in a variety of tumor tissues. Therefore, they have been used as target genes for some tumor therapies. However, the differential expressions of the p16, p53, and pcna genes in human sarcomas and their effects on prognosis have not been widely reported.
METHODS: The Oncomine dataset was used to analyze the transcription levels of p16, p53, and pcna genes, and the gene expression profile interactive analysis (GEPIA) dataset was used to analyze the differential expressions of p16, p53, and pcna. The expression levels of p16, p53, and pcna were further analyzed by Western Blotting. GEPIA and Kaplan-Meier analyses were used to analyze the prognostic value of p16, p53, and pcna. Furthermore, p16, p53, and pcna gene mutations and their association with overall survival (OS) and disease-free survival (DFS) were analyzed using cBioPortal datasets. In addition, genes co-expressed with p16, p53, and pcna were analyzed using Oncomine. The DAVID dataset was used to analyze the functional enrichment of p16, p53, pcna, and their co-expressed genes by Gene Ontology (GO) and Metascape were used to construct a network map. Finally, the immune cell infiltration of p16, p53, and pcna in patients with sarcoma was reported by Tumor Immune Estimation Resource (TIMER).
RESULTS: p16, p53, and pcna were up-regulated in human sarcoma tissues and almost all sarcoma cell lines. Western Blotting showed that the expression of p16, p53, and pcna was elevated in osteosarcoma cell lines. The expression of pcna was correlated with OS, the expression of p16, p53, and pcna was correlated with relapse-free survival, and the genetic mutation of p16 was negatively correlated with OS and DFS. We also found that p16, p53, and pcna genes were positively/negatively correlated with immune cell infiltration in sarcoma.
CONCLUSIONS: The results of this study showed that p16, p53, and pcna can significantly affect the survival and immune status of sarcoma patients. Therefore, p16, p53, and pcna could be used as potential biomarkers of prognosis and immune infiltration in human sarcoma and provide a possible therapeutic target for sarcoma.