Autophagy-related risk signature based on CDNK2A to facilitate survival prediction of patients with endometrial cancer

IF 3.2 4区医学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Journal of Gene Medicine Pub Date : 2024-01-06 DOI:10.1002/jgm.3648

Chaomin Yue, Baohua Lin, Xiang Sun, Xindi Xu, Chufan Zhou, Jiaying Fan

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Abstract

Background

Autophagy plays an important role in immunity and inflammation. The present study aimed to explore the prognostic significance of autophagy-related genes (ARGs) in endometrial cancer (EC) using bioinformatics.

Methods

The list of ARGs was obtained from the Human Autophagy Database. The differentially expressed ARGs (DEARGs) between the EC and normal endometrial tissue samples were screened from The Cancer Genome Atlas database. Cox regression analysis was performed on the DEARGs to screen the prognostic ARGs and construct risk signatures for overall survival (OS) and progression-free survival (PFS). The hub ARGs were identified from a protein–protein interaction network, and CDKN2A was obtained from the intersection of prognostic ARGs and hub ARGs. The association of CDKN2A expression with clinical characteristics and immune infiltration were analyzed. Finally, the role of CDKN2A in autophagy was confirmed in EC cell lines.

Results

CDKN2A, PTK6 and DLC1 were used to establish risk signatures for predicting the survival of EC patients. Receiver operating characteristic curve analysis indicated that the risk signatures can accurately predict both OS and PFS. CDKN2A was the only hub prognostic ARG, and showed significant association with the age, survival status, grade, histological type, body mass index and FIGO (i.e. International Federation of Gynecology and Obstetrics) stage (p < 0.05). Furthermore, CDKN2A expression was also correlated with the infiltration of immune cells, indicating that CDKN2A might play a critical role in regulating the immune microenvironment and immune responses in EC. In addition, silencing of CDKN2A gene promoted autophagy in the HEC-1A cell line and upregulated the expression levels of autophagy-related proteins.

Conclusions

CDKN2A is a prognostic factor and therapeutic target in EC, and is likely associated with the tumor immune landscape and autophagy.

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基于 CDNK2A 的自噬相关风险特征有助于预测子宫内膜癌患者的生存率

背景自噬在免疫和炎症中发挥着重要作用。本研究旨在利用生物信息学方法探讨自噬相关基因（ARGs）在子宫内膜癌（EC）中的预后意义。方法 ARGs 列表来自人类自噬数据库。从癌症基因组图谱（The Cancer Genome Atlas）数据库中筛选出子宫内膜癌组织样本与正常子宫内膜组织样本之间差异表达的ARGs（DEARGs）。对 DEARGs 进行 Cox 回归分析，筛选出预后 ARGs，并构建出总生存期（OS）和无进展生存期（PFS）的风险特征。从蛋白质-蛋白质相互作用网络中确定了中心ARGs，并从预后ARGs和中心ARGs的交叉点中获得了CDKN2A。分析了CDKN2A的表达与临床特征和免疫浸润的关系。最后，在 EC 细胞系中证实了 CDKN2A 在自噬中的作用。结果 CDKN2A、PTK6 和 DLC1 被用于建立预测心肌梗死患者生存率的风险特征。接收操作特征曲线分析表明，风险特征能准确预测OS和PFS。CDKN2A是唯一的枢纽预后ARG，并与年龄、生存状态、分级、组织学类型、体重指数和FIGO（即国际妇产科联盟）分期有显著相关性（p <0.05）。此外，CDKN2A的表达还与免疫细胞的浸润相关，这表明CDKN2A可能在调节EC的免疫微环境和免疫反应中起着关键作用。此外，沉默 CDKN2A 基因可促进 HEC-1A 细胞系的自噬，并上调自噬相关蛋白的表达水平。结论 CDKN2A 是 EC 的预后因子和治疗靶点，可能与肿瘤免疫环境和自噬有关。

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来源期刊

Journal of Gene Medicine 医学-生物工程与应用微生物

CiteScore

6.40

自引率

0.00%

发文量

审稿时长

6-12 weeks

期刊介绍： The aims and scope of The Journal of Gene Medicine include cutting-edge science of gene transfer and its applications in gene and cell therapy, genome editing with precision nucleases, epigenetic modifications of host genome by small molecules, siRNA, microRNA and other noncoding RNAs as therapeutic gene-modulating agents or targets, biomarkers for precision medicine, and gene-based prognostic/diagnostic studies. Key areas of interest are the design of novel synthetic and viral vectors, novel therapeutic nucleic acids such as mRNA, modified microRNAs and siRNAs, antagomirs, aptamers, antisense and exon-skipping agents, refined genome editing tools using nucleic acid /protein combinations, physically or biologically targeted delivery and gene modulation, ex vivo or in vivo pharmacological studies including animal models, and human clinical trials. Papers presenting research into the mechanisms underlying transfer and action of gene medicines, the application of the new technologies for stem cell modification or nucleic acid based vaccines, the identification of new genetic or epigenetic variations as biomarkers to direct precision medicine, and the preclinical/clinical development of gene/expression signatures indicative of diagnosis or predictive of prognosis are also encouraged.