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.