Diagnostic role of collagen-III and matrix metalloproteinase-1 for early detection of hepatocellular carcinoma.

Background: As the poor prognosis of hepatocellular carcinoma (HCC) is mostly due to late detection at an advanced stage there is a strong need for establishing more effective strategies for early identification. We hypothesized that collagen-III and matrix metalloproteinase-1 (MMP-1) and their ratio (CMR) are effective markers for identifying early-HCC when used alongside serum AFP, alkaline phosphatase and bilirubin.Methods: We recruited 148 patients with HCC, 133 with cirrhosis and 121 with fibrosis. Liver fibrosis was staged according to METAVIR, HCC was diagnosed by on histological findings or typical imaging characteristics by ultrasound and computed tomography. Collagen-III and MMP-1 were identified based on Western blotting and quantified in sera using ELISA, liver function tests (LFTs) by routine methods.Results: Patients with HCC showed a significantly (P < 0.05) higher collagen-III and collagen-III/MMP-1 ratio (CMR) than fibrotic and cirrhotic patients. Patients with HCC showed significantly (P < 0.05) lower concentration of MMP-1 than those without. As expected, numerous LFTs were also abnormal. A score of AFP, alkaline phosphatase and bilirubin together with CMR (the HCC-ABC test) was then constructed, This yielded ROC area under curves of 0.85 (95% CI 0.79-0.98) for identifying small tumour size (<3 cm), 0.87 (0.79-0.98) for identifying CLIP (0-1) [Cancer of the Liver Italian Program] disease severity, and 0.87 (0.74-0.93) for identifying BCLC disease severity (all p < 0.001), which is each case exceeded the predictive value of AFP.Conclusion: HCC-ABC diagnostic Test is a promising index for HCC early detection with a high degree of accuracy that may facilitate therapy.

Clinical value of a diagnostic score for colon cancer based on serum CEA, CA19-9, cytokeratin-1 and mucin-1.

BACKGROUND: Although established markers such as CEA and CA19-9 are important for diagnosing early stages of colon cancer, they are not ideal. Developing promising markers include cytokeratin 1 (CK1) and mucin-1 (MUC1), but the combined value of each of these markers is unclear. We therefore evaluated the value of a combined laboratory-based score of these four markers in the diagnosis of colon cancer. METHODS: Two hundred patients who had undergone colonoscopic examination (150 colon cancer, 50 benign growths) were recruited. The study was controlled by 35 healthy subjects. CEA, CA19-9, CK1 and MUC1 were measured by ELISA and evaluated for cancer diagnosis using area under the receiver operating characteristic curve (AUC). RESULTS: Serum levels of all four markers were increased in the order colon cancer > benign disease > healthy controls (p < 0.001). In multivariate analysis, CA19.9 (p = 0.025), CK1 (p < 0.001) and MUC1 (p = 0.009) were significant independent predictors of colon cancer. A score that gave the greatest power of discrimination for colon cancer was defined as 1.06 + [0.001 × CA19.9 result] + [0.003 × CEA result] + [0.03 × CK1 result] + [0.05 × MUC1 result]. The colon score provided superior discrimination, AUC, and sensitivity and specificity for colon cancer versus benign growth than each of the individual markers. Similarly, the colon score provided superior AUC, and sensitivity and specificity that each individual marker for tumour stage, lymph node invasion and distant organ metastases than each individual marker. CONCLUSION: A colon score derived from serum CEA, CA19-9, CK1 and MUC1 is a potential valuable non-invasive index that could be used for detection and screening early stage colon cancer patients.

A rapid, low-cost quantitative diagnostic method for hepatitis C virus infection using capillary zone electrophoresis.

Hepatitis C virus (HCV)-RNA amplification is a costly procedure in terms of time and reagents. Consequently, the search for more a cost-effective specific HCV diagnostic method is of great interest. Capillary zone electrophoresis (CZE) methods that detect HCV in serum, plasma, whole blood, and ascites without the need for sample pretreatment are not currently available. Here, a CZE method was developed that detects a larger specific peak in serum and other body fluids of HCV-infected patients than that found in healthy or hepatitis B virus (HBV)-infected individuals. The nature of the HCV peak was investigated using biochemical treatments, including RNase, DNase, and chymotrypsin enzymes. Electroeluted HCV peak was applied to transmission electron microscopy; electron micrographs showed that the HCV peak was attributed to virus-like particles with diameter and morphological properties similar to non-enveloped HCV nucleocapsids. The determination of CZE-HCV and HCV-RNA levels using quantitative real-time reverse transcriptase-polymerase chain reaction (qRT-PCR) in 258 subjects revealed that these two tests were highly correlated (r = 0.92, p < 0.0001). One important issue of HCV testing is the storage conditions of serum to obtain reliable results. Serum samples at -20 °C showed the best preservation of the HCV peak up to one year. In conclusion, we detected HCV using CZE in a microliters volume from different body fluids. Besides the stability of samples in maintaining their peak height, the HCV-CZE test is rapid (<15 min) and a well-suited and low-cost technique. Thus, a major improvement in the quantitative diagnosis of HCV infection was established.

HCC-ART score, a simple, highly sensitive and specific test for early diagnosis of hepatocellular carcinoma: a large-scale, multicentre study.

BACKGROUND: A simple scoring system is needed to discriminate HCC from patients with chronic liver diseases (CLD). The simplest score would be one that requires only variables that can be documented simply from routine laboratory tests without the need for sophisticated tests. METHODS: Data from the estimation group (1351 patients) and the validation group (2208 patients) were retrospectively analysed. Liver fibrosis-negative control and liver cirrhosis were compared with HCC. Area under ROC curve (AUC) were used to develop HCC-α-fetoprotein-routine test (HCC-ART). RESULTS: Hepatocellular carcinoma-AFP-routine test showed diagnostic accuracy for liver cirrhosis vs HCC with ROC curves of 0.99%, sensitivity of 97%, and specificity of 96% in the estimation, and 0.95%, 90%, and 83%, respectively, in the validation. Sensitivity (97%) and specificity (100%) were obtained to discriminate HCC from liver fibrosis. Area under curve for AFP at 400 U l(-1) was 0.70, sensitivity was 41%, and specificity was 99% in the estimation, and 0.77%, 54%, and 99%, respectively, in the validation. The AUC for HCC-ART in HCC with single tumour, absent vascular invasion, size <2 cm and CLIP score (0-1) were 0.95, 0.93, 0.86, 0.87, respectively, compared with 0.72, 0.71, 0.71, 0.50, respectively, for AFP. CONCLUSION: Hepatocellular carcinoma-AFP-routine test could increase the accuracy of HCC screening and surveillances and could be used worldwide without extra efforts.