[The expression of YTHDF2 in cervical lesions and its relationship with prognosis based on bioinformatics].
<b>Objective:</b> To investigate the role of YTHDF2 in cervical lesions and its potential molecular mechanism. <b>Methods:</b> Gene expression data of cervical tissue were obtained from the GEO database to analyze the expression of <i>YTHDF2</i> 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 <i>YTHDF2</i> mRNA was detected by reverse transcription real-time polymerase chain reaction. The expression of <i>YTHDF2</i> in cervical lesions and the mediating role of HPV infection in the relationship between <i>YTHDF2</i> and squamous intraepithelial lesion (SIL) were evaluated. <i>YTHDF2</i>-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 <i>YTHDF2</i> and prognosis. <b>Results:</b> Compared with normal cervical tissue, <i>YTHDF2</i> was highly expressed in cervical lesion tissue (<i>P</i><0.05). A total of 3 672 differentially expressed genes were screened from the dataset GSE49339. Gene Ontology analysis showed that <i>YTHDF2</i> was mainly involved in transcription regulation. Kyoto Encyclopedia of Genes and Genomes analysis showed that <i>YTHDF2</i> might be related to HPV infection and other signaling pathways. In the mediation analysis, <i>χ</i><sup>2</sup> test results showed that the expression level of <i>YTHDF2</i> was significantly different among groups (<i>χ</i><sup>2</sup>=22.47, <i>P</i><0.001). Trend <i>χ</i><sup>2</sup> test further showed that the expression level of <i>YTHDF2</i> was upregulated with the degree of cervical precancerous lesions (trend <i>χ</i><sup>2</sup>=10.26, <i>P</i>=0.001). Multivariate logistic regression analysis indicated that high <i>YTHDF2</i> expression increased the risk of low-grade squamous intraepithelial lesions (<i>OR</i>=3.15, 95%<i>CI</i>: 1.93-5.15) and high-grade squamous intraepithelial lesions (<i>OR</i>=1.85, 95%<i>CI</i>: 1.01-3.39). Mediation effect analysis revealed a partial mediating effect of HPV infection between <i>YTHDF2</i> and SIL, accounting for 32.02% of the total effect. Twelve <i>YTHDF2</i> related genes were screened by the intersection of multiple datasets. The immune infiltration analysis results showed that <i>YTHDF2</i> and related genes <i>KLF4</i>, <i>E2F3</i> and <i>HOXC6</i> were associated with immune infiltration (all <i>P</i><0.05). Multivariate Cox proportional hazard regression model analysis showed that low expression of <i>KLF4</i> (<i>HR</i>=0.53, 95%<i>CI</i>: 0.30-0.94) and high expression of <i>RHOB</i> (<i>HR</i>=1.80, 95%<i>CI</i>: 1.04-3.13) were risk factors for the prognosis of cervical cancer. <b>Conclusion:</b> <i>YTHDF2</i> 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.
Authors
- Zhiqiang Tian (ORCID: https://orcid.org/0000-0003-4147-3149)
- Lei Ding (ORCID: https://orcid.org/0000-0003-4869-8877)
- Weihong Zhao (ORCID: https://orcid.org/0000-0002-9645-7499)
- Xing Lin Feng (ORCID: https://orcid.org/0000-0003-3588-1859)
- Z X Ran (ORCID: https://orcid.org/0009-0001-3014-641X)
- Jintao Wang (ORCID: https://orcid.org/0000-0001-5958-1194)
- Rongrong Zhang (ORCID: https://orcid.org/0000-0002-1228-9345)
- Ning Tian (ORCID: https://orcid.org/0000-0001-6341-5316)
- Yujia Peng
Institutions
- Shanxi Medical University (CN)
- Second Hospital of Shanxi Medical University (CN)
Publication Details
- Journal
- PubMed
- Published
- 2025-02-10
- DOI
- https://doi.org/10.3760/cma.j.cn112338-20240819-00509
- Primary Topic
- Cancer-related molecular mechanisms research
- Type
- article