Methylated Septin9: biomarker for diagnosis of cervical cancer in cervical scrapings and for prediction of pelvic lymphatic metastasis in plasma

Abstract BackgroundAberrant Septin9 methylation in cervical cancer has been rarely studied. In this study we aimed to identify its diagnostic value of cervical cancer in cervical scrapings, and its predictive potential in plasma for pelvic nodal metastasis of cervical cancer.MethodsThe statuses of methylated Septin9 in fresh cervical lesions were first evaluated by using quantitative methylation-specific PCR(qMS-PCR). Subsequently 248 samples of cervical scrapings were collected to explore Septin9 methylation in different severities of cervical lesions; and the relationship between Septin9 methylation in plasma and pelvic nodal metastasis of cervical cancer was further evaluated.ResultsMethylated Septin9 was detected in all cancerous tissues, but not in cervicitis controls (P < 0.0001). The degrees of Septin9 methylation increased with growing severity of cervical lesions in cervical scrapings (P < 0.0001). Methylation analysis of Septin9 demonstrated a satisfactory specificity and area under the curve(AUC) in cervical cancer detection, at an equivalent sensitivity relative to any other test. And methylated Septin9 also yielded a high specificity and AUC in detecting high-grade squamous intraepithelial lesion or cervical cancer(≥ HSIL). Plasma-based Septin9 methylation had a high discriminatory power in predicting pelvic nodal metastasis, with an optimal specificity of 81.48%; additionally an increasing sensitivity from 50% to nearly 80% was found when combined with squamous cell carcinoma antigen(SCC-Ag). ConclusionsIn conclusion, we demonstrated methylated Septin9 to be an innovative diagnostic biomarker for cervical cancer in cervical scrapings and its non-invasive predictive potential in plasma for pelvic nodal metastasis of cervical cancer.