Aberrant single‐minded homolog 1 methylation as a potential biomarker for cervical cancer

Abstract

BackgroundThe aim of this study is to evaluate the possibility of using the methylation status of single‐minded homolog 1 (SIM1) as a diagnostic biomarker for cervical cancer.MethodsAll the patient and normal specimens including the normal cervix (n = 10), cervical cancer tissues (n = 45), blood (n = 45), and cervical brush specimens (n = 110) were retrospectively obtained. Quantitative methylation‐specific PCR was performed to detect SIM1 methylation in primary tumors, cervical brush specimens, and plasma circulating cell‐free DNA (ccfDNA). SIM1 expression was detected by western blot analysis.ResultsWe found that SIM1 was highly methylated in the majority of the cervical cancer tissues that we tested, but not in any of the normal tissues. Hypermethylation of SIM1 led to a pronounced reduction in SIM1 expression in cervical cancer tissues compared with normal cervix. SIM1 methylation status on cervical brush specimens also distinguished cervical cancer from normal, cervical intraepithelial neoplasia (CIN) 1 and 2. The degree of SIM1 methylation was significantly associated with the severity of the disease (Ptrend < .0001). We also investigated the possibility of detecting methylated SIM1 in plasma ccfDNA from cervical cancer patients. Methylated SIM1 was detected in 36.6% (15/41) of ccfDNA samples, and concordance rate with the matched cancer tissues was 41.5% (17/41) with sensitivity 38.5% and specificity 100%.ConclusionThis study has shown that SIM1 is frequently hypermethylated in cervical cancer, compared with normal cervix tissue, CIN1 and 2 samples, suggesting that the methylation status of SIM1 could be a potential diagnostic biomarker for cervical cancer.

Diagnostic value of circulating tumor DNA as an effective biomarker in cervical cancer: a meta-analysis

“…Ten of 15 included studies had selected circulating HPV DNA as a detected gene target. Other gene targets had higher sensitivity but lower specificity, including SIM1 methylation [26], MEG3 methylation [28], Bmi-1 [29], miR-21 [30], and hsa-miR-92a [31].…”

“…Two studies [10,24] increased the risk of bias owing to a lack of patient selection. Four studies [25][26][27][28] did not mention the use of a blinding method or reference standard, which may have resulted in an unknown risk of bias in the meta-analysis.…”

“…Two studies [10,27] used Taqman PCR, and another three studies [29][30][31] used reverse transcription PCR. Additionally, two studies [17,32] used droplet digital PCR (ddPCR), and three studies [24,26,28] used methylation-specific (MSP) PCR. Only one study [33] used nested PCR.…”

“…Circulating HPV DNA or viral-cellular junction was detected in six studies [10,17,24,27,32,33]. Other target genes were also different, such as Bmi-1 mRNA [29], miR-21 [30], PIK3CA mutations [34], hsa-miR-92a [31], and SIM1 methylation [26]. Nine of the studies extracted ctDNA from plasma, and the other six studies extracted DNA from serum.…”

The detection of DNA methylation of tumour suppressor genes in cervical high‐grade squamous intraepithelial lesion: A prospective cytological‐histological correlation study of 70 cases

“…Recently, DNA methylation has been suggested as one of the epigenetic changes participating in carcinogenesis . In cervical cancer and high‐grade squamous intraepithelial lesion (HSIL), the DNA methylation status of some 30 genes have so far been studied . The exact role of this mechanism and the order of events leading to the development of carcinoma are unknown.…”