Department of Gynecology, Guangdong Women and Children Hospital, 521 Xing Nan Road, Guangzhou, 511400, Guangdong Province, China.
Guangdong Women and Children Hospital of Guangzhou Medical University, Guangzhou, China.
BMC Cancer. 2018 Nov 29;18(1):1182. doi: 10.1186/s12885-018-4877-5.
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.
Cervical 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.
(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).
FAM19A4 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.
探索 FAM19A4 甲基化在 HPV 高危型阳性的中国妇女宫颈样本中的诊断价值，以评估宫颈癌或其癌前病变。
采用宫颈涂片法收集 215 例 HPV 高危型感染的妇女宫颈样本。我们有目的地选择 61 例宫颈癌患者、57 例高级别鳞状上皮内病变（HSIL）患者、31 例低级别鳞状上皮内病变（LSIL）患者和 66 例无宫颈上皮内瘤变（CIN）的患者进行组织学确认。采用 Taqman 探针定量 PCR（qPCR）检测宫颈样本中 FAM19A4 的甲基化状态，并进一步评估该基因在宫颈癌诊断中的应用。
（1）随着宫颈病变的进展，FAM19A4 甲基化水平逐渐升高，无 CIN、LSIL、HSIL 和宫颈癌样本的甲基化率分别为 10.61%（7/66）、35.48%（11/31）、56.14%（32/57）和 93.44%（57/61）。（2）在所有 HPV 阳性样本中，HPV16/18 组的 FAM19A4 甲基化水平高于其他 12 种 HPV 组（P<0.05），但将宫颈病变分为宫颈癌、HSIL、LSIL 和无 CIN 组后，两组间无显著差异（P>0.05）。（3）宫颈癌不同临床病理参数间 FAM19A4 甲基化无显著差异。（4）FAM19A4 甲基化试验的敏感性虽低于细胞学和 FAM19A4 联合 HPV16/18 基因分型，但特异性最好，单独检测 HSIL 及≥HSIL 的特异性均为 81.44%，具有良好的约登指数（YI）和曲线下面积（AUC）。
FAM19A4 是宫颈癌前病变的特异性标志物。FAM19A4 甲基化分析可能作为一种辅助筛查方法，用于诊断宫颈（前）癌。但是，考虑到本回顾性研究的局限性，需要进行前瞻性的基于人群的研究，以进一步证实 FAM19A4 甲基化在中国妇女中对宫颈癌（前）病变的诊断价值。
