p16、p53 和 pcna 在肉瘤中的预后价值及免疫浸润的评价。

Prognostic value of p16, p53, and pcna in sarcoma and an evaluation of immune infiltration.

机构信息

Department of Orthopedics, The Second Hospital of Anhui Medical University, 678 Furong Road, Hefei, 230601, China.

出版信息

J Orthop Surg Res. 2022 Jun 10;17(1):305. doi: 10.1186/s13018-022-03193-3.

DOI:10.1186/s13018-022-03193-3

PMID:35689249

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9185979/

Abstract

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.

摘要

背景

p16、p53 和增殖细胞核抗原（pcna）基因在许多染色质修饰中发挥重要作用，并且在各种肿瘤组织中发现高度表达。因此，它们已被用作某些肿瘤治疗的靶基因。然而，p16、p53 和 pcna 基因在人类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

使用 Oncomine 数据集分析 p16、p53 和 pcna 基因的转录水平，使用基因表达谱交互式分析（GEPIA）数据集分析 p16、p53 和 pcna 的差异表达。通过 Western Blotting 进一步分析 p16、p53 和 pcna 的表达水平。使用 GEPIA 和 Kaplan-Meier 分析评估 p16、p53 和 pcna 的预后价值。此外，使用 cBioPortal 数据集分析 p16、p53 和 pcna 基因的突变及其与总生存期（OS）和无病生存期（DFS）的关系。此外，使用 Oncomine 分析与 p16、p53 和 pcna 共表达的基因。使用 DAVID 数据集通过基因本体论（GO）分析 p16、p53、pcna 及其共表达基因的功能富集，使用 Metascape 构建网络图。最后，通过肿瘤免疫估计资源（TIMER）报告肉瘤患者中 p16、p53 和 pcna 的免疫细胞浸润。

结果

p16、p53 和 pcna 在人类肉瘤组织和几乎所有肉瘤细胞系中上调。Western Blotting 显示 p16、p53 和 pcna 在骨肉瘤细胞系中的表达升高。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 的遗传突变与 OS 和 DFS 呈负相关。我们还发现 p16、p53 和 pcna 基因与肉瘤中免疫细胞浸润呈正/负相关。