scholarly journals Diagnostic Value of the Methylation of Multiple Gene Promoters in Serum in Hepatitis B Virus-Related Hepatocellular Carcinoma

2017 ◽  
Vol 2017 ◽  
pp. 1-6 ◽  
Author(s):  
Xueyan Dong ◽  
Qiang Hou ◽  
Yueming Chen ◽  
Xianjun Wang

This study sought to evaluate the diagnostic value of the methylation of multiple gene promoters in serum in hepatitis B virus- (HBV-) related hepatocellular carcinoma (HCC). A total of 343 participants were enrolled, including 98 patients with HCC, 75 patients with liver cirrhosis (LC), 90 patients with chronic hepatitis B (CHB), and 80 healthy individuals. RASSF1A, APC, BVES, TIMP3, GSTP1, and HOXA9 were selected as the candidate genes. The MethyLight method was used to assay promoter methylation statuses. The diagnostic performances of markers were assessed by constructing receiver operating characteristic (ROC) curves. The prevalences of methylation for RASSF1A, APC, BVES, HOXA9, GSTP1, and TIMP3 were 52.04%, 36.73%, 29.59%, 20.41%, 17.35%, and 11.22%, respectively. APC methylation completely overlapped with RASSF1A methylation. The area under the curve (AUC) for RASSF1A methylation (0.718) was better than the corresponding AUC for AFP (0.609) in distinguishing HCC from CHB. When RASSF1A, BVES, HOXA9, and AFP were combined, the AUC was 0.852 (95% CI = 0.796–0.908, P=0.028), and the sensitivity and specificity were 83.7% and 78.9%, respectively. In conclusion, an assay that combines methylation of the RASSF1A, BVES, and HOXA9 gene promoters in serum and AFP could significantly improve HBV-related HCC diagnoses.

2020 ◽  
Vol 318 (2) ◽  
pp. G305-G312 ◽  
Author(s):  
Zhu Zhan ◽  
Yalan Guan ◽  
Kenley Mew ◽  
Weiqiong Zeng ◽  
Mingli Peng ◽  
...  

Hepatocellular carcinoma (HCC) is the sixth common malignant tumor worldwide, but current efficient and convenient screening methods remain lacking. This study aimed to discover a diagnostic or a screening biomarker from the urine of hepatitis B virus (HBV)-related HCC patients. We used iTRAQ coupled with mass spectrometry to identify candidate urinary proteins in a discovery cohort ( n = 40). The selected proteins were confirmed using ELISA in a validation cohort ( n = 140). Diagnostic performance of the selected proteins was assessed using receiver operating characteristic (ROC) and qualitative diagnostic analysis. A total of 96 differentially expressed proteins were identified. Urinary α-fetoprotein (u-AFP) and orosomucoid 1 (u-ORM1) were selected as target proteins by bioinformatics analysis and were significantly higher in HCC than in non-HCC patients, as validated by Western blot analysis and ELISA. u-AFP had a strong correlation with serum AFP-L3 (Pearson’s r = 0.944, P < 0.0001), indicating that u-AFP may be derived from circulating blood. The area under the curve (AUC) of u-AFP was 0.795 with a sensitivity of 62.5% and a specificity of 95.4%, which showed no significantly difference with serum AFP (se-AFP). The AUC was 0.864 as u-AFP and u-ORM1 were combined, and they performed much better than u-AFP or u-ORM1 alone. Qualitative diagnostic analysis showed that the positive predictive value of u-AFP was 90.1% and the diagnostic sensitivity of parallel combination of u-AFP and u-ORM1 was 85.1%. Taken together, AFP and ORM1 in the urine may be used as a diagnostic or screening biomarker of HCC, and studies on large samples are needed to validate the result. NEW & NOTEWORTHY This study provides a novel way to find biomarkers of hepatocellular carcinoma (HCC) and a new perspective of α-fetoprotein clinical application. The urine reagent strips may be helpful in high epidemic areas of HCC and in low-resource settings.


Pathology ◽  
2012 ◽  
Vol 44 (4) ◽  
pp. 318-324 ◽  
Author(s):  
Hui Chen ◽  
Ling-yu Sun ◽  
Hong-qun Zheng ◽  
Qi-fan Zhang ◽  
Xiao-ming Jin

2020 ◽  
Vol 252 (4) ◽  
pp. 297-307
Author(s):  
La-Mei Chen ◽  
Lin Xiang ◽  
Wei-Juan Sun ◽  
Yu-Jia Zhai ◽  
Shuai Gao ◽  
...  

2021 ◽  
Vol 67 (03/2021) ◽  
Author(s):  
Bohui Ouyang ◽  
Qing-Qing Xie ◽  
Wenjie Huang ◽  
Linchun Wang ◽  
Shifu Tang ◽  
...  

2019 ◽  
Vol 48 (3) ◽  
pp. 030006051988927
Author(s):  
Ting Song ◽  
Lili Wang ◽  
Bin Su ◽  
Weiping Zeng ◽  
Taiyi Jiang ◽  
...  

Objective This study aimed to explore the use of different combinations of alpha-fetoprotein (AFP), Lens culinaris agglutinin-reactive AFP (AFP-L3), and des-gamma-carboxyprothrombin (DCP) for the early diagnosis of hepatocellular carcinoma (HCC) in patients with hepatitis B virus (HBV)-associated liver cirrhosis (LC). Methods There were 167 subjects, including 100 with HCC and 67 with LC, who were enrolled into this study. Serum AFP, AFP-L3, and DCP levels were detected by chemiluminescent enzyme immunoassay and analyzed using the receiver operating characteristics (ROC) method. Results The sensitivity and specificity of AFP and DCP for differentiating between early HCC and HBV-associated LC were 51.5% and 92.5%, and 60.0% and 84.7%, respectively. Comparative analysis of ROC curves showed no significant difference in the area under the curve (AUC) for AFP and DCP. Moreover, the combination of AFP and DCP showed the largest AUC value with a diagnostic sensitivity and specificity of 67% and 83.1%, respectively. Conclusion These results suggest that AFP is the best single biomarker for distinguishing between HBV-associated LC and early HCC induced by HBV. However, the combination of AFP and DCP can enhance the diagnostic value of AFP for differentiating between these diseases.


2020 ◽  
Author(s):  
Juanjuan Chen ◽  
Dongling Tang ◽  
Chu Xu ◽  
Zhili Niu ◽  
Huan Li ◽  
...  

Abstract Objective To evaluate the potential diagnostic value of growth differentiation factor 15 (GDF15) alone and its combination with protein induced by vitamin K absence-II (PIVKA-II) and alpha-fetoprotein (AFP) for hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC). Methods Serum levels of GDF15, PIVKA-II, and AFP were measured in 110 patients with HBV-associated HCC, 70 patients with HBV-related liver cirrhosis (LC), 70 patients with chronic hepatitis B (CHB), and 110 healthy patients. Results Serum GDF15 was positively related to the levels of PIVKA-II and AFP in patients with HCC (r = 0.352 and r = 0.378; all P &lt;.0001). When the receiver operating characteristic (ROC) curve was plotted for patients with HCC vs all control patients, serum GDF15 had diagnostic parameters of an area under the curve (AUC) of 0.693, a sensitivity of 67.30%, and a specificity of 66.70%, which were lower than parameters for PIVKA-II and AFP (all P &lt;.0001). When the ROC curve was plotted for patients with HCC vs patients with LC, the combination of GDF15 and PIVKA-II had the highest diagnostic accuracy of AUC and specificity as compared with other combinations (all P &lt;.0001). Conclusion We found that GDF15 is a potent serum marker for the detection of HBV-associated HCC and that PIVKA-II combined with GDF15 can improve diagnostic accuracy for HBV-associated HCC.


2020 ◽  
Author(s):  
Cheng Peng ◽  
Zhuonan Li ◽  
Zishan Xie ◽  
Zhanpeng Wang ◽  
Yanshuo Ye ◽  
...  

Abstract Background: Alpha-fetoprotein (AFP) has been widely used for many years as a serum marker for hepatocellular carcinoma (HCC). However, AFP has been recognized as having poor sensitivity. More and more studies have concluded that circulating microRNAs (miRNAs) might be a promising biomarker that could complement AFP. However, the diagnostic ability of circulating miRNAs has varied among the studies. Therefore, we performed the present meta-analysis to appraise the diagnostic performance of circulating miRNAs as a biomarker for hepatitis B virus-associated HCC (HBV-HCC) patients with low AFP levels. Methods: We performed a systematic review and meta-analysis of the published literature to assess the diagnostic accuracy of circulating miRNAs in differentiating HBV-HCC patients with low AFP levels from non-HCC controls. Results: Circulating miRNAs showed promising potential in the diagnosis of HBV-HCC patients with low AFP levels. In the low-AFP HBV-HCC patients, the area under the curve (AUC) was 0.88 (95% confidence interval [CI]: 0.84–0.90). The pooled sensitivity and specificity were 0.84 (95% CI: 0.78–0.88) and 0.76 (95% CI: 0.69–0.83), respectively. Conclusions: The detection of circulating miRNAs provides a valuable method for the diagnosis of HBV-HCC in patients with low AFP levels.


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