Quantitative DNA methylation analysis of paired box gene 1 and LIM homeobox transcription factor 1 α genes in cervical cancer

Abstract

Abstract. DNA methylation is associated with tumorigenesis and may act as a potential biomarker for detecting cervical cancer. The aim of the present study was to explore the methylation status of the paired box gene 1 (PAX1) and the LIM homeobox transcription factor 1 α (LMX1A) gene in a spectrum of cervical lesions in an Eastern Chinese population. This single-center study involved 121 patients who were divided into normal cervix (NC; n=28), low-grade squamous intraepithelial lesion (LSIL; n=32), high-grade squamous intraepithelial lesion (HSIL; n=34) and cervical squamous cell carcinoma (CSCC; n=27) groups, according to biopsy results. Following extraction and modification of the DNA, quantitative assessment of the PAX1 and LMX1A genes in exfoliated cells was performed using pyrosequencing analysis. Receiver operating characteristic (ROC) curves were generated to calculate the sensitivity and specificity of each parameter and cut-off values of the percentage of methylation reference (PMR) for differentiation diagnosis. Analysis of variance was used to identify differences among groups. The PMR of the two genes was significantly higher in the HSIL and CSCC groups compared with that in the NC and LSIL groups (P<0.001). ROC curve analysis demonstrated that the sensitivity, specificity and accuracy for detection of CSCC were 0.790, 0.837 and 0.809, respectively, using PAX1; and 0.633, 0.357 and 0.893, respectively, using LMX1A. These results indicated that quantitative PAX1 methylation demonstrates potential for cervical cancer screening, while further investigation is required to determine the potential of LMX1A methylation.

DNA Methylation and Hydroxymethylation in Cervical Cancer: Diagnosis, Prognosis and Treatment

“…Mersakova et al (2018) and Rong et al (2019) have recently shown that CADM1 is a potential biomarker for cervical cancer. There was a significant difference in the promoter Kan et al, 2014;Lai et al, 2014;Kong et al, 2015;Nikolaidis et al, 2015;Xu et al, 2015Xu et al, , 2018Chen et al, 2016;Liou et al, 2016;Huang et al, 2017;Fang et al, Lee et al, 2006;Yeon et al, 2018 methylation of plasma CADM1 and its D-dimer between healthy individuals and those with cervical cancer. Combining these factors to predict metastasis revealed high specificity (90.5%) and sensitivity (80.4%) (Rong et al, 2019).…”

“…Hypermethylated PAX1 is important in cancer progression (Huang et al, 2017) that functions in regulating cellular differentiation and proliferation (Fang et al, 2019). PAX1 can be used to detect cervical squamous cell carcinoma (CSCC) in 121 patients from eastern China with 80.9, 83.7, and 79.0% accuracy, specificity, and sensitivity, respectively (Xu et al, 2018). Combining methylated PAX1 and the presence of HPV16/18 results in an 89.2 and 76.0% sensitivity and specificity, respectively in detecting CIN3 + (Liou et al, 2016).…”

“…Thus, Sp1 and EZH2 may work in concert to regulate LMX1A expression (Lin et al, 2013). The sensitivity, specificity, and accuracy of the detection of cervical cancer are 63.3, 35.7, and 89.3%, respectively using LMX1A (Xu et al, 2018). However, another group have used LMX1A methylation to detect CIN3 + in samples with moderate sensitivity (77%) and specificity (88%) (Lai et al, 2010).…”

The role of HPV‑induced epigenetic changes in cervical carcinogenesis (Review)

“…Other cellular genes, such as ADCYAP1, MAL (a T-cell differentiation protein) and CADM1 are also silenced in cells derived from UCC, due to hypermethylation of their promoters, and this condition is associated with a greater risk of tumor progression (49). Moreover, PAX1 cell genes, which encode the transcription factor paired box 1, SOX1 for the sex determining region Y-box 1 and LMX1A for LIM homeobox transcription factor 1α, all of which are involved in controlling cell division and differentiation, showed significantly higher methylation levels of their promoters in UCC cells when compared to normal cervical tissues (50,51). Finally, the RARβ gene, which is usually expressed in normal epithelial tissue, acts as a tumor suppressor when interacting with its ligand to inhibit cell migration (52).…”

Methylenetetrahydrofolate Dehydrogenase 1 Silencing Expedites the Apoptosis of Non-Small Cell Lung Cancer Cells via Modulating DNA Methylation

“…When the CpG sequence of some tumor suppressor genes CpG island is hypermethylation, it can increase the degree of chromosome helix and silencing and deletion of tumor suppressor gene, thereby inducing tumor growth [ 13 , 14 ]. Increasing evidence illustrates that DNA methylation is involved in the occurrence of tumor, and it is an important biomarker to measure various tumors [ 15 – 17 ].…”