| Summary: | Aim: We investigated whether a difference exists between <i>TSHR, PTEN</i> and <i>RASSF1A</i> methylation status in plasma of subjects with papillary thyroid cancer (PTC). Methods: Peripheral blood samples were collected from 68 patients with PTC and 86 healthy controls (HC). Thyroid cancer tissue and corresponding adjacent normal tissue methylation levels were analyzed. DNA methylation level changes in <i>TSHR, PTEN</i> and <i>RASSF1A</i> genes were analyzed by quantitative methylation-sensitive polymerase chain reaction. Results: We observed that the methylation level of <i>TSHR</i> was significantly higher in the thyroid cancer tissue compared to adjacent normal tissue (<i>p</i> = 0.040). <i>TSHR</i> methylation levels in the PTC group plasma samples were significantly higher compared to HC (<i>p</i> = 0.022). After surgery, PTC plasma samples showed lower <i>TSHR</i> and <i>PTEN</i> methylation levels compared to the levels before surgery (<i>p</i> = 0.003, <i>p</i> = 0.031, respectively). The <i>TSHR</i> methylation level was significantly higher in PTC with larger tumor size (>2 cm) (<i>p</i> < 0.001), and lymph node metastases (<i>p</i> = 0.01), lymphovascular invasion (<i>p</i> = 0.02) and multifocality (<i>p</i> = 0.013) 0ROC analysis revealed that the <i>TSHR</i> methylation level provides high accuracy in distinguishing PTC from HC (<i>p</i> = 0.022, AUC of 0.616). Conclusion: <i>TSHR</i> methylation in peripheral blood samples is expected to be a sensitive and specific minimally invasive tool for the diagnosis of PTC, especially in combination with other diagnostic means.
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