| 彭煜舒,田楠,冯新琳,张瑞,冉朝霞,王金桃,赵卫红,田志强,丁玲.基于生物信息学分析YTHDF2在宫颈病变中的表达及其与预后的关系[J].中华流行病学杂志,2025,46(2):280-287 |
| 基于生物信息学分析YTHDF2在宫颈病变中的表达及其与预后的关系 |
| The expression of YTHDF2 in cervical lesions and its relationship with prognosis based on bioinformatics |
| 收稿日期:2024-08-19 出版日期:2025-02-14 |
| DOI：10.3760/cma.j.cn112338-20240819-00509 |
| 中文关键词: 宫颈病变 人乳头瘤病毒 RNA甲基化 生物信息学 |
| 英文关键词: Cervical lesion Human papillomavirus RNA methylation Bioinformatic |
| 基金项目:国家自然科学基金（81703313）；山西省自然科学研究（20210302123308）；山西省高等教育“百亿工程”科技引导专项（BYBLD002） |
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| 中文摘要: |
| 目的 分析YTHDF2在宫颈病变及预后中的作用及其潜在分子机制。方法 从GEO数据库获取宫颈组织基因表达数据，以分析YTHDF2 mRNA表达情况并进行通路富集分析。选取山西省介休市妇幼保健院妇科门诊通过液基薄层细胞检测技术确诊的宫颈病变患者作为研究对象，收集宫颈病变相关资料和宫颈脱落细胞。采用导流杂交法检测HPV感染状况，反转录实时定量聚合酶链式反应测定YTHDF2 mRNA表达水平，分析YTHDF2在宫颈病变中的表达及HPV感染在YTHDF2与宫颈鳞状上皮内病变（SIL）中的中介作用。对GEO和ENCORI数据库多数据集取交集筛选YTHDF2相关基因，分析相关基因表达情况，并对其进行免疫浸润分析及生存分析，以评价YTHDF2与预后的关系。结果 与正常宫颈相比，YTHDF2在宫颈病变组织中高表达（P<0.05）。GSE49339数据集共筛选出3 672个差异表达基因，基因本体论分析结果显示，YTHDF2主要参与转录调控等过程；基因组百科全书分析发现YTHDF2可能与HPV感染等信号通路有关。在中介分析中，χ²检验结果显示，YTHDF2表达水平在各组间差异有统计学意义（χ2=22.47，P<0.001），趋势χ²检验结果显示，YTHDF2表达水平在宫颈癌前病变中随病变程度增加而上调（趋势χ2=10.26，P=0.001），多因素logistic回归分析结果显示，YTHDF2高表达增加了低级别鳞状上皮内病变（OR=3.15，95%CI：1.93~5.15）和高级别鳞状上皮内病变（OR=1.85，95%CI：1.01~3.39）的发生风险，且HPV感染在YTHDF2与SIL中存在部分中介效应，占总效应的32.02%。多数据集取交集筛选出12个YTHDF2相关基因，免疫浸润分析结果显示，YTHDF2及其相关基因KLF4、E2F3和HOXC6与免疫浸润相关（均P<0.05）；多因素Cox比例风险回归模型分析结果显示，KLF4低表达（HR=0.53，95%CI：0.30~0.94）和RHOB高表达（HR=1.80，95%CI：1.04~3.13）为宫颈癌预后的危险因素。结论 YTHDF2在宫颈病变中高表达，可能参与调控HPV感染相关过程，其下游相关基因与宫颈癌免疫浸润和预后生存相关，可为宫颈病变相关机制研究提供理论依据。 |
| 英文摘要: |
| Objective To investigate the role of YTHDF2 in cervical lesions and its potential molecular mechanism. Methods Gene expression data of cervical tissue were obtained from the GEO database to analyze the expression of YTHDF2 mRNA and perform pathway enrichment analysis. Patients with cervical lesions diagnosed by thinprep cytologic test in Gynecological Outpatient Department of Maternal and Child Health Hospital in Jiexiu, Shanxi Province, were selected as the research subjects. Data of cervical lesions and cervical exfoliated cells were collected. HPV infection status was detected by flow-through hybridization, and the expression of YTHDF2 mRNA was detected by reverse transcription real-time polymerase chain reaction. The expression of YTHDF2 in cervical lesions and the mediating role of HPV infection in the relationship between YTHDF2 and squamous intraepithelial lesion (SIL) were evaluated. YTHDF2-related genes were screened from multiple datasets in the GEO and ENCORI databases, and their expression, immune infiltration, and survival analysis were performed to assess the association between YTHDF2 and prognosis. Results Compared with normal cervical tissue, YTHDF2 was highly expressed in cervical lesion tissue (P<0.05). A total of 3 672 differentially expressed genes were screened from the dataset GSE49339. Gene Ontology analysis showed that YTHDF2 was mainly involved in transcription regulation. Kyoto Encyclopedia of Genes and Genomes analysis showed that YTHDF2 might be related to HPV infection and other signaling pathways. In the mediation analysis, χ2 test results showed that the expression level of YTHDF2 was significantly different among groups (χ2=22.47, P<0.001). Trend χ2 test further showed that the expression level of YTHDF2 was upregulated with the degree of cervical precancerous lesions (trend χ2=10.26, P=0.001). Multivariate logistic regression analysis indicated that high YTHDF2 expression increased the risk of low-grade squamous intraepithelial lesions (OR=3.15, 95%CI: 1.93-5.15) and high-grade squamous intraepithelial lesions (OR=1.85, 95%CI: 1.01-3.39). Mediation effect analysis revealed a partial mediating effect of HPV infection between YTHDF2 and SIL, accounting for 32.02% of the total effect. Twelve YTHDF2 related genes were screened by the intersection of multiple datasets. The immune infiltration analysis results showed that YTHDF2 and related genes KLF4, E2F3 and HOXC6 were associated with immune infiltration (all P<0.05). Multivariate Cox proportional hazard regression model analysis showed that low expression of KLF4 (HR=0.53, 95%CI: 0.30-0.94) and high expression of RHOB (HR=1.80, 95%CI: 1.04-3.13) were risk factors for the prognosis of cervical cancer. Conclusion YTHDF2 is highly expressed in cervical lesions and may have been involved in the regulation of HPV infection-related pathways and its downstream related genes are related to immune infiltration and prognosis of cervical cancer, providing a theoretical basis for the study of mechanisms related to cervical lesions. |
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