Significance of Hypermethylation of Tumor-Suppressor Genes PTGER4 and ZNF43 at CpG Sites in the Prognosis of Colorectal Cancer

Abstract

The status of DNA methylation in primary tumor tissue and adjacent tumor-free tissue is associated with the occurrence of aggressive colorectal cancer (CRC) and can aid personalized cancer treatments at early stages. Tumor tissue and matched adjacent nontumorous tissue were extracted from 208 patients with CRC, and the correlation between the methylation levels of PTGER4 and ZNF43 at certain CpG loci and the prognostic factors of CRC was determined using the MassARRAY System testing platform. The Wilcoxon signed-rank test, a Chi-square test, and McNemar’s test were used for group comparisons, and Kaplan–Meier curves and a log-rank test were used for prediction. The hypermethylation of PTGER4 at the CpG_4, CpG_5, CpG_15, and CpG_17 tumor tissue sites was strongly correlated with shorter recurrence-free survival (RFS), progression-free survival (PFS), and overall survival (OS) [hazard ratio (HR) = 3.26, 95% confidence interval (CI) = 1.38–7.73 for RFS, HR = 2.35 and 95% CI = 1.17–4.71 for PFS, HR = 4.32 and 95% CI = 1.8–10.5 for OS]. By contrast, RFS and PFS were significantly longer in the case of increased methylation of ZNF43 at the CpG_5 site of normal tissue [HR = 2.33, 95% CI = 1.07–5.08 for RFS, HR = 2.42 and 95% CI = 1.19–4.91 for PFS]. Aberrant methylation at specific CpG sites indicates tissue with aggressive behavior. Therefore, the differential methylation of PTGER4 and ZNF43 at specific loci can be employed for the prognosis of patients with CRC.

Expression of CKS2 in Hepatocellular Carcinoma: Correlation with Survival Outcomes and Immune Microenvironment

“…Compared with normal tissues, the methylation level of gene methylation sites in cancer tissues is significantly abnormal, which is not only related to gene expression, but also related to tumor prognosis. [34][35][36] So we used SMART dataset to study the LIHC samples from TCGA. The results revealed significantly different methylation levels of five CpG sites, cg14307853 is hypermethylated, whereas cg13651859, cg24622726, cg00292435, and cg00922328 are hypomethylated in CKS2 in HCC when compared with normal tissues (Figure 4A and Supplementary Figure 1).…”

An Overview: Genetic Tumor Markers for Early Detection and Current Gene Therapy Strategies

“…Therefore, hypermethylation of the tumor suppressor gene can be a strong progression marker of cancer. 45 , 46 Several methods are in use for the detection of methylation as a biomarker with their advantages and disadvantages. Some of the methods are cost-effective but of medium or low sensitivity.…”

Biomarker Discoveries and Potential Biomarkers in Lung Cancer : A Narrative Review

“…Hypermethylation in the promoters of APC, SFRP1, SFRP2, SFRP5, WIF1, DKK3, ITIH5, and RASSF1A is associated with breast cancer growth (Feng et al, 2010) and epigenetics in APC and RSSF1A genes are biomarkers in early detection of breast cancer (Cao et al, 2018;Coyle et al, 2007;Kloten et al, 2013). Hypermethylation is seen in the PTGER4 and ZNF43 promoters in colorectal patients compared to normal tissue leading to shorter survival followed up to 5 years (Chen et al, 2022). In another research, cancer growth can be characterized by hypermethylation of the TSGs (Baylin and Jones, 2011;Esteve-Puig et al, 2020;Hon et al, 2012;Tavares et al, 2022) in the CAV1 (Li et al, 2015, p. 48), CDH13 (Feng et al, 2010), ID4 (Umetani et al, 2005), and SCGB3A1 (Benevolenskaya et al, 2016) genes.…”