Urine α-fetoprotein and orosomucoid 1 as biomarkers of hepatitis B virus-associated hepatocellular carcinoma

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.

Download Full-text

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

Disease Markers ◽

10.1155/2017/2929381 ◽

2017 ◽

Vol 2017 ◽

pp. 1-6 ◽

Cited By ~ 9

Author(s):

Xueyan Dong ◽

Qiang Hou ◽

Yueming Chen ◽

Xianjun Wang

Keyword(s):

Hepatocellular Carcinoma ◽

Hepatitis B Virus ◽

Hepatitis B ◽

Area Under The Curve ◽

Roc Curves ◽

Diagnostic Value ◽

Gene Promoters ◽

Multiple Gene ◽

B Virus ◽

Better Than

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.

Download Full-text

The role of circulating microRNAs for the diagnosis of hepatitis B virus-associated hepatocellular carcinoma with low alpha-fetoprotein level: A systematic review and meta-analysis

10.21203/rs.3.rs-16340/v2 ◽

2020 ◽

Author(s):

Cheng Peng ◽

Zhuonan Li ◽

Zishan Xie ◽

Zhanpeng Wang ◽

Yanshuo Ye ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Systematic Review ◽

Hepatitis B Virus ◽

Hepatitis B ◽

Meta Analysis ◽

Area Under The Curve ◽

Alpha Fetoprotein ◽

Circulating Mirnas ◽

Circulating Micrornas ◽

B Virus

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.

Download Full-text

The role of circulating microRNAs for the diagnosis of hepatitis B virus-associated hepatocellular carcinoma with low alpha-fetoprotein level: a systematic review and meta-analysis

BMC Gastroenterology ◽

10.1186/s12876-020-01345-5 ◽

2020 ◽

Vol 20 (1) ◽

Author(s):

Cheng Peng ◽

Zhuonan Li ◽

Zishan Xie ◽

Zhanpeng Wang ◽

Yanshuo Ye ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Systematic Review ◽

Hepatitis B Virus ◽

Hepatitis B ◽

Meta Analysis ◽

Area Under The Curve ◽

Alpha Fetoprotein ◽

Circulating Mirnas ◽

Circulating Micrornas ◽

B Virus

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.

Download Full-text

The role of circulating microRNAs for the diagnosis of hepatitis B virus-associated hepatocellular carcinoma with low alpha-fetoprotein level: A systematic review and meta-analysis

10.21203/rs.3.rs-16340/v1 ◽

2020 ◽

Author(s):

Cheng Peng ◽

Zhuonan Li ◽

Zishan Xie ◽

Zhanpeng Wang ◽

Yanshuo Ye ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Systematic Review ◽

Hepatitis B Virus ◽

Hepatitis B ◽

Meta Analysis ◽

Area Under The Curve ◽

Alpha Fetoprotein ◽

Circulating Mirnas ◽

Circulating Micrornas ◽

B Virus

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.

Download Full-text

Role of environmental factors in the etiology of hepatocellular carcinoma

Orvosi Hetilap ◽

10.1556/oh.2010.28913 ◽

2010 ◽

Vol 151 (28) ◽

pp. 1132-1136 ◽

Cited By ~ 7

Author(s):

István Tornai

Keyword(s):

Hepatocellular Carcinoma ◽

Hepatitis B Virus ◽

Environmental Factors ◽

Hepatitis B ◽

Hepatitis A ◽

Virus Hepatitis ◽

B Virus

A krónikus vírushepatitisek jelentik ma a legismertebb okokat a hepatocellularis carcinoma (HCC) kialakulásában. A krónikus B- és C-vírus-hepatitis a májrákok körülbelül 40-50%-át okozza. A nyugati típusú társadalmakban a HCC előfordulása folyamatosan növekvő tendenciát mutat. Az alkohol számít a környezeti tényezők közül a legfontosabbnak, bár az alkoholfogyasztás a legtöbb országban csökken. Ez aláhúzza az egyéb környezeti tényezők fontosságát is. Az elfogyasztott alkoholmennyiséggel egyenes arányban növekszik a cirrhosis és a következményes HCC gyakorisága nőkben és férfiakban egyaránt. A kémiai anyagok közül a legismertebb a Kínában és Afrikában elterjedt aflatoxin, amely a gabonaféléket szennyező mycotoxin. Hasonló területeken endémiás, mint a hepatitis B-vírus, együtt szinergista hatást fejtenek ki. A dohányzás is egyértelműen bizonyított hepatocarcinogen hatással rendelkezik. Ez is jelentősen fokozódik, ha alkoholfogyasztással vagy vírushepatitisszel társul. Társadalmilag talán a legfontosabb az elhízás, a következményes nem alkoholos zsírmáj, illetve steatohepatitis és a 2-es típusú cukorbetegség, amelyek prevalenciája egyre fokozódik. Feltehetően ezek állnak a növekvő HCC-gyakoriság hátterében. Az inzulinrezisztencia és az oxidatív stressz képezik a legfontosabb patogenetikai lépéseket a májsejtkárosodásban. További fontos rizikótényező az orális fogamzásgátlók elterjedt használata. Egyes foglalkozások esetén a tartós szervesoldószer-expozíció is növeli a HCC rizikóját. Védelmet jelenthetnek az antioxidánsok, a szelén, a gyógyszerek közül a statinok és a feketekávé-fogyasztás.

Download Full-text