Abstract
BackgroundThe association between SOX14 and cancer has been reported. The aim of this study was to identify and validate the potential value of SOX14 methylation in the early detection of cervical cancer.MethodsFirst, we extracted the data for SOX14 methylation and expression within cervical cancer from The Cancer Genome Atlas (TCGA) database and analysed them via UALCAN, Wanderer, MEXPRESS and LinkedOmics. Subsequently, according to the bioinformatics findings, primers and probes were designed for the most significantly differentiated methylation CpG site and synthesized for methylation-specific PCR (MSP) and quantitative methylation-specific PCR (QMSP) to verify SOX14 methylation in both cervical tissuses and liquid-based cell samples. Eventually, the clinical diagnostic efficacy of SOX14 methylation in the normal, cervical intraepithelial neoplasia, and cancer groups was analysed by ROCAUC.ResultsPooled analysis demonstrated that SOX14 methylation levels were significantly increased in cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) compared to normal tissues (P < 0.001). Both the verification and validation cohorts indicated that the methylation level and the positive rate of SOX14 gradually increased with increasing severity from normal to cancer samples (P < 0.01). When the cut-off value was set as 128.45, the sensitivity and specificity of SOX14 hypermethylation in the diagnosis of cervical cancer were 94.12 and 86.46%, respectively. When taken as a screening biomarker (>CINII), the sensitivity was 74.42% and the specificity was 81.48%, with a cut-off value of 10.37.ConclusionSOX14 hypermethylation is associated with cervical cancer and has the potential to be a molecular biomarker for the screening and early diagnosis of cervical cancer.
Highlights
The association between SOX14 and cancer has been reported
Regarding human papillomavirus (HPV) tests, despite the superior sensitivity, Zhao et al BMC Cancer (2021) 21:675 the lower specificity is an inevitable problem leading to a need to identify innovative biomarkers for cervical cancer screening [7]
The dataset from Wanderer demonstrated that the mean methylation level of each CpG site in the whole SOX14 gene was significantly increased in Cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) compared to normal tissues (Fig. 1c) (P < 0.05)
Summary
The aim of this study was to identify and validate the potential value of SOX14 methylation in the early detection of cervical cancer. Cervical cancer ranks as the fourth most frequently diagnosed cancer and the fourth leading cause of cancer death among women, with an estimated 604,000 cases and 342,000 deaths worldwide in 2020 [1] It is the second most common type of cancer in women in the Southeast Asia region and a major cause of cancer death among women in low- and middle-income countries (LMICs) [2]. Most of the techniques on DNA methylation detection are generally easy to perform, less labour intensive and repeatable. For those reasons, the identification and performance of cancer-related DNA hypermethylation biomarkers in clinical settings have attracted the attention of clinical practitioners and researchers
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