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MYB原癌基因样2被鉴定为子宫内膜癌的生物标志物:来自生物信息学和临床验证的证据。

MYB Proto-Oncogene Like 2 identified as a biomarker for uterine corpus endometrial carcinoma: evidence from bioinformatics and clinical validation.

作者信息

Lu Jiaoyun, Luo Furong

机构信息

Department of Oncology, Xi'an NO.3 Hospital, The Affiliated Hospital of Northwest University, Xi'an, Shaanxi, China.

Department of Traditional Chinese Medicine, Xi'an NO.3 Hospital, The Affiliated Hospital of Northwest University, Xi'an, Shaanxi, China.

出版信息

Front Oncol. 2025 May 13;15:1595485. doi: 10.3389/fonc.2025.1595485. eCollection 2025.

Abstract

BACKGROUND

Endometrial carcinoma (EC) is the sixth most prevalent malignancy among women globally, posing a significant clinical challenge due to limited therapeutic options for advanced or recurrent cases. The identification of novel prognostic biomarkers and therapeutic targets is crucial for improving patient outcomes. This study aimed to investigate the multifaceted roles of MYB Proto-Oncogene Like 2 (MYBL2) in uterine corpus endometrial carcinoma (UCEC).

METHODS

We employed multiple bioinformatics algorithms (GEPIA, TCGA, TIMER2.0) to analyze MYBL2 expression across different cancer types and in UCEC specifically. Expression patterns were validated using quantitative real-time PCR (qPCR) on clinical samples. Epigenetic analyses focused on promoter methylation status, and immune infiltration patterns were assessed using MethSurv, CIBERSORT and TIMER2.0. Drug sensitivity profiling was performed using the CPADS web platform.

RESULTS

MYBL2 was found to be significantly upregulated in UCEC tumors compared to normal tissues. Elevated MYBL2 expression correlated with advanced histologic grade and clinical stage, indicating its potential as a biomarker for disease progression. Epigenetic analysis revealed promoter hypomethylation in tumors, suggesting a regulatory mechanism driving MYBL2 overexpression. MYBL2 demonstrated dynamic interactions with the tumor immune microenvironment, including associations with immune cell infiltration patterns and co-expression with immune checkpoint molecules and chemokines. Drug sensitivity profiling highlighted differential therapeutic responses linked to MYBL2 expression levels.

CONCLUSION

This study establishes MYBL2 as a critical regulator of UCEC progression, bridging epigenetic dysregulation, immune modulation, and clinical outcomes. The findings provide a foundation for exploring MYBL2-targeted strategies in precision immunotherapy and personalized therapeutic interventions.

摘要

背景

子宫内膜癌(EC)是全球女性中第六大最常见的恶性肿瘤,由于晚期或复发病例的治疗选择有限,构成了重大的临床挑战。识别新的预后生物标志物和治疗靶点对于改善患者预后至关重要。本研究旨在探讨MYB原癌基因样2(MYBL2)在子宫体子宫内膜癌(UCEC)中的多方面作用。

方法

我们采用多种生物信息学算法(GEPIA、TCGA、TIMER2.0)分析MYBL2在不同癌症类型以及特异性在UCEC中的表达。使用定量实时PCR(qPCR)对临床样本进行表达模式验证。表观遗传学分析聚焦于启动子甲基化状态,并使用MethSurv、CIBERSORT和TIMER2.0评估免疫浸润模式。使用CPADS网络平台进行药物敏感性分析。

结果

与正常组织相比,发现MYBL2在UCEC肿瘤中显著上调。MYBL2表达升高与高级别组织学分级和临床分期相关,表明其作为疾病进展生物标志物的潜力。表观遗传学分析揭示肿瘤中启动子低甲基化,提示驱动MYBL2过表达的调控机制。MYBL2与肿瘤免疫微环境表现出动态相互作用,包括与免疫细胞浸润模式的关联以及与免疫检查点分子和趋化因子的共表达。药物敏感性分析突出了与MYBL2表达水平相关的不同治疗反应。

结论

本研究确立MYBL2为UCEC进展的关键调节因子,连接表观遗传失调、免疫调节和临床结果。这些发现为探索精准免疫治疗和个性化治疗干预中以MYBL2为靶点的策略奠定了基础。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9736/12106007/821a04769bb7/fonc-15-1595485-g001.jpg

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