The diagnostic value of serum DSA-TRF in hepatocellular carcinoma.

TRF is a glycoprotein mainly secreted by hepatocytes, The aim of this study was to explore the diagnostic value of aberrant glycosylated serum transferrin (TRF) especially containing multi-antennary glycans in hepatocellular carcinoma (HCC).A total of 581 subjects including HCC patients, liver cirrhosis (LC) patients, chronic hepatitis (CHB) patients and healthy controls (HC) were recruited. All the subjects were randomly assigned to training group (n = 411) and validation group (n = 170). We firstly analyzed the serum protein N-glycome profiling of HCC, LC, and HC by DNA sequencer-assisted fluorophore-assisted carbohydrate electrophoresis (DSA-FACE) technology. We established a lectin-antibody sandwich ELISA (Lectin-ELISA) method to detect multi-antennary glycans-contained TRF (DSA-TRF) in serum, in which Datura stramonium Agglutinin (DSA) was used for specific recognition. Levels of serum DSA-TRF and TRF were analyzed respectively. The diagnostic efficacies of DSA-TRF and TRF of differentiating HCC patients from CHB, LC patients and HC within the training group were evaluated using receiver operating characteristic (ROC) curve and tested in the validation group.The result found that in training group, serum TRF and DSA-TRF levels differed significantly between HCC (1.86 ± 0.50, g/L, 0.285 ± 0.06), CHB + LC (2.39 ± 0.74, g/L, 0.189 ± 0.07) and HC (1.92 ± 0.69, g/L, 0.249 ± 0.09) (HCC vs. CHB + LC, P < 0.001; HCC vs. HC, P < 0.001; CHB + LC vs. HC, P < 0.001). The area under the ROC curve (AUC) of DSA-TRF was significantly superior to AFP (0.880, 95%CI: 0.834-0.925 vs. 0.776, 95%CI: 0.725-0.827, P = 0.003) in differentiating HCC from CHB + LC. The AUC of diagnostic model GlycoTRF1 (0.981, 95%CI: 0.969-0.993) was higher than DSA-TRF and AFP alone (P<0.001) in differentiating HCC from CHB + LC, which was verified in validation group.The results indicated that the serum DSA-TRF might serve as a potential glycan biomarker for distinguishing HCC from CHB and LC.

Clinical evaluation of hepatitis B core-related antigen in chronic hepatitis B and hepatocellular carcinoma patients.

BACKGROUND: Hepatitis B core-related antigen (HBcrAg) has been revealed as an important marker of Hepatitis B virus (HBV) infection recently. We aimed to evaluate the HBcrAg assay for indication of HBV loads in chronic hepatitis B (CHB) and hepatocellular carcinoma (HCC) patients and assess the association between HBcrAg/cccDNA and HCC recurrence. METHODS: HBcrAg was measured by chemiluminescence enzyme immunoassay. Intrahepatic covalently closed circular DNA (cccDNA) was measured by real-time PCR with TaqMan fluorescent probes based on liver specimens from 89 HCC patients. RESULTS: HBcrAg correlated positively with HBV DNA irrespective of HBeAg status. Both HBcrAg and HBV DNA were associated with cccDNA in patients with elevated serum HBV DNA (>4 log IU/mL). In patients with non-elevated HBV DNA (≤4 log IU/mL), no relationship between HBV DNA and cccDNA was observed, but we still documented a modest correlation between HBcrAg and cccDNA. Finally, the recurrence-free survival rates were significantly lower in HCC patients with high intrahepatic cccDNA and serum HBcrAg levels than those with low cccDNA/HBcrAg levels (p = 0.035, p = 0.003 respectively). CONCLUSIONS: HBcrAg not only can serve as a biomarker to assess HBV loads in patients as well as provide a good method for monitoring cccDNA in HCC, but also can be used as a good prognostic predictor for HCC patients.

A Nomogram Predicting Extrahepatic Metastases for Patients with Adjuvant Transarterial Chemoembolization after Hepatectomy.

Background: Prognosis remains poor for hepatocellular carcinoma (HCC) patients with extrahepatic metastases (EHMs). This study aimed to develop a nomogram to predict EHMs in HCC patients who underwent adjuvant transarterial chemoembolization (TACE) following hepatectomy. Methods: Data of 578 HCC patients who underwent TACE after hepatectomy at the Eastern Hepatobiliary Surgery Hospital was retrospectively reviewed. Cox regression analyses was used to select variables to construct the nomogram. Predictive accuracy and discriminative ability of the model were performed using concordance index (C-index), calibration curve and the area under time-dependent receiver operating characteristic (ROC) curve. Results: Postoperative EHMs were detected in 89 and 31 patients in the training cohort (n = 453) and validation cohort (n = 125), respectively. Multivariate analysis showed that tumor size (HR, 1.099; 95% CI, 1.049-1.152), coarse beam type of tumor histopathological structure (HR, 2.382; 95% CI, 1.030-5.512), presence of satellite nodules (HR, 1.936; 95% CI, 1.156-3.244) and alpha-fetoprotein (AFP) (HR, 1.399; 95% CI, 1.098-1.783) were independent risk factors for EHMs (all p < 0.05). The nomogram incorporated these factors achieved good agreement between prediction and actual observation with a concordance index (C-index) of 0.73 (95% CI, 0.68 to 0.78) and 0.71 (95% CI, 0.63 to 0.79) in the training cohort and validation cohort, respectively. In addition, patients who had a nomogram score > 17 were considered to have higher risk for EHMs compared with those scored ≤ 12. Furthermore, the time-dependent area under the ROC curve indicated comparative stability and adequate discriminative ability of the model. Conclusions: This novel nomogram can identify those with high risk of EHMs after adjuvant TACE following hepatectomy. The validation cohort showed a good performance, suggesting it could benefit surgeons on decision-making.

Distribution features and controls of heavy metals in surface sediments from the riverbed of the Ningxia-Inner Mongolian reaches, Yellow River, China.

Fifty-six riverbed surface sediment (RSS) samples were collected along the Ningxia-Inner Mongolian reaches of the Yellow River (NIMYR). These samples were analyzed to determine their heavy metal concentrations (Co, Cr, Ni, Cu, V and Zn), grain sizes, sediment sources and the causes of their heavy metal contamination. The cumulative distribution functions of the heavy metals in RSS of these reaches are plotted to identify the geochemical baseline level (GBL) of each element and determine the average background concentration of each heavy metal. Principal component analysis and hierarchical cluster analysis are conducted based on the grain sizes of RSS, and the samples are classified into two groups: coarse grained samples (CGS) and fine grained samples (FGS). The degree of heavy metal contamination for each sample is identified by its enrichment factor (EF). The results reveal that the coarse particle component (medium sand and coarse sand) in the bed materials is chiefly from the bordering deserts along the Yellow River. The clay and silt in the bed materials chiefly originate from the upper reaches of the Yellow River, and the fine sand is identified as a hybrid sediment derived from the upper reaches of the Yellow River and the bordering deserts. The CGS primarily appear in the reaches bordering deserts, and the sites are near the confluence of gullies and the Yellow River. The FGS are located adjacent to cities with especially strong industrial activity such as Wuhai, Bayan Nur, Baotou and Togtoh. The Cr, Ni, Cu, V and Zn concentrations (mg kg(-1)) are 84.34 ± 49.46, 30.21 ± 7.90, 25.01 ± 7.61, 73.17 ± 18.92 and 55.62 ± 18.93 in the FGS and 65.07 ± 19.51, 23.86 ± 6.84, 18.04 ± 3.8, 53.47 ± 10.57 and 34.89 ± 9.19 in the CGS respectively, and the concentrations of Co in the CGS (213.40 ± 69.71) are notably higher than in the FGS (112.02 ± 48.87) and greater than the Co GBL (210). The most contaminated samples in the NIMYR are adjacent to the cities of Wuhai (EF(Cr) = 5.19; EF(Ni) = 1.96), Bayan Nur (EF(Cr) = 5.88; EF(Ni )= 2.08) and Baotou (EF(Cu) = 1.55; EF(Zn) = 1.68) where the Cr, Ni, Cu, V and Zn concentrations are above the correlated GBLs (85, 34, 27, 75 and 62 mg kg(-1), respectively), which are mostly affected by industrial processes, and samples that are only moderately contaminated by heavy metals are found in the reaches bordering desert (Wuhai-Baotou) because contaminated sediments are diluted by uncontaminated desert sand. In contrast, all of the Cu, Cr, Ni, V and Zn concentrations in RSS of the Qingtongxia-Wuhai reach are lower than the correlated GBLs of elements.