| Autor: |
Singh, Alka, Gupta, Sameer, Badarukhiya, Jaydeep A., Sachan, Manisha |
| Předmět: |
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| Zdroj: |
International Journal of Cancer; Sep2020, Vol. 147 Issue 6, p1740-1752, 13p |
| Abstrakt: |
Accumulated evidence revealed that aberrant CpG island hypermethylation plays an important role in carcinogenesis which can serve as a promising target for molecular detection in body fluids. Despite a myriad of attempts to diagnose ovarian cancer (OC) at an early stage, this clinical aim remains a major challenge. To date, no single biomarker is able to accurately detect early OC in either tissue or body fluid. Aberrant DNA methylation patterns in circulating DNA provide highly specific cancer signals. In our study, we establish a novel panel of methylation‐specific genes for the development of a TaqMan based qPCR assay to quantify methylation levels. We analyzed promoter methylation of homeobox A9 (HOXA9) and hypermethylated in cancer 1 (HIC1) quantitatively in 120 tissue samples and in 70 matched serum cell‐free DNA (CFDNA) of cancerous and noncancerous samples by MethyLight assay. HOXA9 and HIC1 methylation occurred in 82.3 and 80.0% of OC tissue samples in singleplex assay, thereby confirming that methylation was highly cancer‐specific. When either or both gene promoter showed methylation, the sensitivity was 88.2% with a specificity of 88.6% in tissue samples. The combined sensitivity for this novel marker panel in serum CFDNA was 88.9% (area under the curve [AUC] = 0.95). In contrast, no hypermethylation was observed in serum from matched cancer‐free control women. Our results confirm the elevated performance of novel epigenetic marker panel (HOXA9 and HIC1) when analyzed in tissue and matched serum samples. Our findings reveal the potential of this biomarker panel as a suitable diagnostic serum biomarker for early screening of OC. What's new? In ovarian cancer, numerous tumor suppressor genes have been shown to be silenced by promoter hypermethylation and associated with disease features. However, few studies have examined concurrent methylation of multiple genes. Harnessing cell‐free DNA as a promising minimally‐invasive tool, here the authors report the development of a biomarker panel for the simultaneous detection of promoter methylation of HOXA9 and HIC1 suppressor genes in a blood‐based assay. The panel achieved enhanced sensitivity and specificity in distinguishing individuals with ovarian cancer from controls. Overall, the study provides a proof of principle that serum DNA methylation markers could help detect early ovarian cancer. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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