Abstract
BackgroundTo explore the diagnostic value of FAM19A4 methylation in high-risk human papilloma virus (hrHPV)-positive cervical samples from Chinese women for estimating cervical cancer or its precancerous lesions.MethodsCervical samples from 215 women infected with high-risk HPV were collected by smear testing. We purposely chose 61 patients with cervical cancer, 57 with high-grade squamous intraepithelial lesions (HSIL), 31 with low-grade squamous intraepithelial lesions (LSIL), and 66 without cervical intraepithelial neoplasia (CIN) after histological confirmation. Taqman probe-based quantitative PCR (qPCR) was utilized to detect the methylation status of FAM19A4 in the cervical samples and further evaluate the use of this gene in the diagnosis of cervical cancer.Results(1) An increasing level of FAM19A4 methylation was detected with increasing progression of cervical lesions, with methylation rates of 10.61%(7/66), 35.48%(11/31), 56.14%(32/57) and 93.44%(57/61) in no CIN, LSIL, HSIL and cervical carcinoma samples respectively. (2) In all hrHPV-positive samples, the levels of FAM19A4 methylation in HPV16/18 groups were higher than that in 12 other hrHPV groups (P < 0.05), but there was no significant difference between two groups after grouping cervical lesions into cervical cancer, HSIL, LSIL and no CIN groups (P>0.05). (3)There were no significant differences of FAM19A4 methylation in different clinicopathological parameters of cervical cancer. (4) Though the sensitivity of FAM19A4 methylation test was inferior to that of cytology and FAM19A4 combining with HPV16/18 genotyping, but showed the best specificity with 81.44% both for detection HSIL alone and ≥ HSIL, with favorable youden index (YI) and area under curve (AUC).ConclusionFAM19A4 is a specific biomarker of cancerous lesions of the cervix. FAM19A4 methylation analysis may serve as an auxiliary screening method for diagnosis of cervical (pre)cancer. However, in consideration of the limitations of this retrospective study, prospective population-based studies are necessary for further confirmation of the diagnostic value of FAM19A4 methylation for detection of cervical (pre)cancer in Chinese women.
Highlights
To explore the diagnostic value of FAM19A4 methylation in high-risk human papilloma virus-positive cervical samples from Chinese women for estimating cervical cancer or its precancerous lesions
In consideration of the limitations of this retrospective study, prospective population-based studies are necessary for further confirmation of the diagnostic value of FAM19A4 methylation for detection of cervicalcancer in Chinese women
In pairwise comparisons between groups, the median methylation scores of FAM19A4 in the high-grade squamous intraepithelial lesions (HSIL), low-grade squamous intraepithelial lesions (LSIL), and no cervical intraepithelial neoplasia (CIN) groups were all lower when compared with the cervical cancer group (P < 0.05)
Summary
To explore the diagnostic value of FAM19A4 methylation in high-risk human papilloma virus (hrHPV)-positive cervical samples from Chinese women for estimating cervical cancer or its precancerous lesions. 94% of cervical cancer results from persistent infection with hrHPV [4, 5]. More than 80% of women become infected with HPV during their lifetime, 90% of which will be effectively cleared by their immune system, with 10% suffering persistent infection, and 1% progressing to cervical cancer [4]. Further screening methods are needed to identify which hrHPV-positive patient has a higher risk of developing cervical cancer or precancerous lesion. Recent studies have found that detecting methylation of related biomarkers maintains the sensitivity and increases the specificity and helps to identify cervical cancer and its precancerous lesions [9, 10]. It is essential to explore more specific cancer biomarkers to identify cervical (pre)cancer
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