International Journal of General Medicine (Jun 2022)
Tumor DNA Methylation Profiles Enable Diagnosis, Prognosis Prediction, and Screening for Cervical Cancer
Abstract
Jiannan Tu,1,* Shengchi Chen,1,* Shizhen Wu,1,* Ting Wu,1,* Renliang Fan,1 Zhixing Kuang2 1Department of Oncology, Nanping First Hospital Affiliated to Fujian Medical University, Nanping, 353000, People’s Republic of China; 2Department of Radiation Oncology, Nanping First Hospital Affiliated to Fujian Medical University, Nanping, 353000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhixing Kuang, Department of Radiation Oncology, Nanping First Hospital Affiliated to Fujian Medical University, Nanping, 353000, People’s Republic of China, Email [email protected]: DNA-methylation-based machine learning algorithms have demonstrated powerful diagnostic capabilities, and these tools are currently emerging in many fields of tumor diagnosis and patient prognosis prediction. This work aimed to identify novel DNA methylation diagnostic biomarkers for differentiating cervical cancer (CC) from normal tissues, as well as a prognostic prediction model to predict survival of CC patients.Methods: The methylation profiles with the available clinical characteristics were downloaded from the Gene Expression Omnibus (GEO) database and The Cancer Genome Atlas (TCGA) program. We first screened out the differential methylation sites in CC and normal tissues and performed multiple statistical analyses to discover DNA methylation diagnostic markers that are used to distinguish CC and normal control. Then, we developed a methylation-based survival model to improve risk stratification.Results: A diagnostic prediction panel consists of five CpG markers that could predict cervical cancer versus normal tissue with highly correct rate of 100%, and cg16428251, cg22341310, and cg23316360 which in diagnostic prediction panel all could yield high sensitivity and specificity for detection of CC and normal in six cohorts (area under curve [AUC] > 0.8), in addition to excellent performance in discriminating between CC and normal sample. The diagnostic marker panel also effectively predicted the CIN3 versus normal tissue with high accuracy in two datasets (AUC = 0.80, 0.789, respectively). Furthermore, a prognostic prediction model aggregated two CpG markers that effectively stratified the prognosis of high-risk and low-risk groups (training cohort: hazard ratio [HR] 4, 95% CI: 1.7– 9.6, P = 0.0021; testing cohort: hazard ratio [HR] 1.9, 95% CI: 1.2– 3.1, P = 0.0072).Conclusion: The findings of our study showed that DNA methylation markers are of great value in the diagnosis and prognosis of CC.Keywords: cervical cancer, DNA methylation, markers, diagnosis, prognosis
