Hypermethylation of SCAND3 and Myo1g Gene Are Potential Diagnostic Biomarkers for Hepatocellular Carcinoma.

Fei Xu,Lulu Zhang,Xiaomeng Ji,Di Song,Jianyong Shao,Yuxia Xu,Wenting He

doi:10.3390/cancers12082332

Abstract

Presently, there is a lack of effective blood-based biomarkers facilitating the diagnosis of hepatocellular carcinoma (HCC). Thus, we aimed to investigate novel methylation markers for HCC diagnosis, and explore relationships between biomarker methylation and clinicopathology of HCC. The methylation status of the SCAN domain containing three (SCAND3) and myosin 1g (Myo1g) genes in HCC cell lines and tissues were detected by digital droplet PCR. The serum SCAND3 and Myo1g methylation levels were analyzed in HCC-afflicted patients and unafflicted controls. The results indicated SCAND3 and Myo1g methylation were abnormally high in the HCC cell lines and tissues. The values of serum SCAND3, Myo1g, and SCAND3 + Myo1g methylation with respect to facilitating the detection, and early detection of HCC were better than for alpha-fetoprotein (AFP) alone. Furthermore, when we combined SCAND3 + Myo1g with AFP, a high sensitivity and specificity resulted. Notably, in the AFP-negative HCC group, the methylation of SCAND3 and Myo1g also showed an excellent diagnostic performance. Besides this, a high serum SCAND3 methylation level was an independent risk factor for predicting portal vein tumor thrombus (PVTT) in HCC patients (OR = 4.746, p = 0.013). Finally, SCAND3 and Myo1g enhanced the HCC diagnostics as noninvasive serum methylation biomarkers, and the SCAND3 methylation status effectively indicated HCC accompanied by PVTT.

Highlights

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths. strategies and outcomes for patients afflicted with hepatocellular carcinoma (HCC) have improved recently, long-term prognoses remain bad, in part because of the lack of effective approaches for early diagnoses [1,2].improving the methods that can be used for the early detection of HCC is a key component for successful treatment and the improvement of survival rates
The results indicated that the SCAN domain containing 3 (SCAND3) and myosin 1g (Myo1g) methylation ratios were significantly higher in HCC tissues than in adjacent noncancerous tissues (p < 0.05, Figure 3)
The results indicated that the serum SCAND3 and Myo1g methylation ratios were significantly higher in HCC-afflicted patients compared to the unafflicted controls

Summary

Introduction

Strategies and outcomes for patients afflicted with HCC have improved recently, long-term prognoses remain bad, in part because of the lack of effective approaches for early diagnoses [1,2]. Improving the methods that can be used for the early detection of HCC is a key component for successful treatment and the improvement of survival rates. Ultrasonography have been the main approaches to screen for HCC. The limitations of AFP and ultrasonography are well recognized and relate to the inadequate sensitivity and specificity for detecting HCC [3,4]. Previous research has indicated that the AFP levels yielded modest measures of sensitivity (39–65%) and specificity (76–94%) [5]. The majority of patients with early-stage HCC are missed during screening based upon their AFP levels alone. Due to Cancers 2020, 12, 2332; doi:10.3390/cancers12082332 www.mdpi.com/journal/cancers

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