基于综合生物信息学分析鉴定HOXB9以预测子宫内膜癌的预后

Identification of HOXB9 to predict prognosis of endometrial cancer based on comprehensive bioinformatics analysis.

作者信息

Xu Yanhua, Zhang Mu, Shi Qin, Cheng Xi, Du Rong, Li Chenglu, Zhang Yuquan

机构信息

Department of Obstetrics and Gynecology, Affiliated Hospital of Nantong University, Medical School of Nantong University, No.20 Xi-Si Road, Nantong, 226001, Jiangsu, China.

Department of Ophthalmology, Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu, China.

出版信息

Eur J Med Res. 2023 Feb 17;28(1):79. doi: 10.1186/s40001-022-00979-3.

DOI:10.1186/s40001-022-00979-3

PMID:36803556

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9936693/

Abstract

BACKGROUND

The HOXB9 gene, which plays a key role in embryonic development, is also involved in the regulation of various human cancers. However, the potential relationship between HOXB9 and endometrial cancer (EC) has not yet been comprehensively analyzed and fully understood.

METHODS

We used multiple bioinformatics tools to explore the role of HOXB9 in EC.

RESULTS

The expression of HOXB9 was significantly upregulated in pan-cancer, including EC (P < 0.05). Quantitative real time polymerase chain reaction (qRT-PCR) experiment confirmed the high expression of HOXB9 in EC from clinical samples (P < 0.001). Double validated by Enrichr and Metascape, HOXB9 showed a strong correlation with HOX family, suggesting that HOX family may also involve in the development of EC (P < 0.05). Enrichment analysis revealed HOXB9 is mainly associated with cellular process, developmental process, P53 signaling pathway, etc. At the single-cell level, the clusters of cells ranked were glandular and luminal cells c-24, glandular and luminal cells c-9, endothelial cells c-15, compared with the other cells. At the genetic level, promoter methylation levels of HOXB9 were significantly higher in tumors than in normal tissues. Furthermore, variations of HOXB9 were closely associated with overall survival (OS) and recurrence free survival (RFS) in EC patients (P < 0.05). The agreement between univariate and multivariate Cox regression indicated that the results were more reliable. Stages III and IV, G2 and G3, tumor invasion ≥ 50%, mixed or serous histological type, age > 60 years, and high expression of HOXB9 were risk factors strongly associated with OS in EC patients (P < 0.05). Therefore, six factors were incorporated to construct a nomogram for survival prediction. Finally, we used the Kaplan-Meier (KM) curve, receiver operating characteristic (ROC) curve, and time-dependent ROC to assess predictive power of HOXB9. KM curve showed EC patients overexpressing HOXB9 had a worse OS. AUC of diagnostic ROC was 0.880. AUCs of time-dependent ROC were 0.602, 0.591, and 0.706 for 1-year, 5-year, and 10-year survival probabilities (P < 0.001).

CONCLUSIONS

Our study provids new insights into the diagnosis and prognosis of HOXB9 in EC and constructs a model that can accurately predict the prognosis of EC.

摘要

背景

HOXB9基因在胚胎发育中起关键作用，也参与多种人类癌症的调控。然而，HOXB9与子宫内膜癌（EC）之间的潜在关系尚未得到全面分析和充分理解。

方法

我们使用多种生物信息学工具来探索HOXB9在EC中的作用。

结果

HOXB9在包括EC在内的泛癌中表达显著上调（P < 0.05）。定量实时聚合酶链反应（qRT-PCR）实验证实临床样本中EC组织中HOXB9高表达（P < 0.001）。经Enrichr和Metascape双重验证，HOXB9与HOX家族显示出强相关性，提示HOX家族可能也参与EC的发生发展（P < 0.05）。富集分析显示HOXB9主要与细胞过程、发育过程、P53信号通路等相关。在单细胞水平，细胞聚类排名为腺上皮和腔上皮细胞c-24、腺上皮和腔上皮细胞c-9、内皮细胞c-15，高于其他细胞。在基因水平，HOXB9的启动子甲基化水平在肿瘤组织中显著高于正常组织。此外，HOXB9的变异与EC患者的总生存期（OS）和无复发生存期（RFS）密切相关（P < 0.05）。单因素和多因素Cox回归分析结果一致，表明结果更可靠。Ⅲ期和Ⅳ期、G2和G3级、肿瘤浸润≥50%、混合或浆液性组织学类型、年龄>60岁以及HOXB9高表达是与EC患者OS密切相关的危险因素（P < 0.05）。因此，纳入六个因素构建了生存预测列线图。最后，我们使用Kaplan-Meier（KM）曲线、受试者工作特征（ROC）曲线和时间依赖性ROC来评估HOXB9的预测能力。KM曲线显示HOXB9过表达的EC患者OS较差。诊断性ROC曲线的AUC为0.880。1年、5年和10年生存概率的时间依赖性ROC曲线的AUC分别为0.602、0.591和0.706（P < 0.001）。