Serum microRNA expression profiling identifies serum biomarkers for HCV-related hepatocellular carcinoma.

BACKGROUND: The identification of high-sensitivity biomarkers for detection of hepatocellular carcinoma (HCC) from high-risk individuals is essential. OBJECTIVE: The present study was undertaken to identify and validate serum microRNAs (miRNAs) as potential biomarkers for hepatitis C virus (HCV)-related HCC. METHODS: Illumina sequencing was employed to screen the expression profiles of miRNAs in serum samples of HCV-related HCC patients and liver cirrhosis (LC) patients. RT-qPCR was used to confirm the altered miRNAs between the two groups. Moreover, candidate miRNAs were examined in serum samples of 40 HCC patients, 54 LC patients, 55 patients with chronic HCV hepatitis and 45 healthy controls. Receiver operating characteristic (ROC) curve analysis was used to evaluate the diagnostic performance of the miRNAs for the detection of HCC. RESULTS: Four miRNAs (miR-122-5p, miR-331-3p, miR-494-3p, miR-224-5p) were significantly increased and two miRNAs (miR-185-5p, miR-23b-3p) were significantly decreased in HCC patients compared to LC patients. ROC curve analysis demonstrated that the six miRNAs could be used as potential biomarkers for HCC detection. Combination of the six miRNAs could efficiently detect HCC in LC patients with the area under the ROC curve (AUC) of 0.995 and combination of the six miRNAs also provided high diagnostic accuracy (AUC = 0.961) for detection of HCC in non-HCC subjects. CONCLUSIONS: The six serum miRNAs can be utilized as a surrogate and non-invasive biomarker for HCV-related HCC diagnosis.

Diagnosis accuracy of serum glypican-3 level in patients with hepatocellular carcinoma: a systematic review with meta-analysis.

BACKGROUND: Previous studies have evaluated the diagnostic value of serum glypican-3 in patients with hepatocellular carcinoma. However, the results remain inconsistent and even controversial. Thus, the aim of the present meta-analysis was to clarify the diagnostic accuracy of serum glypican-3 for hepatocellular carcinoma. METHODS: A meta-analysis including 22 studies was performed with 2325 cases and 2280 controls. Relevant studies were searched in the EMBASE, PubMed, and Web of Science databases, covering relevant papers published until November 1, 2017. The quality of the studies was assessed by revised QUADAS tools. Sensitivity, specificity, and other measures were pooled and determined to evaluate the accuracy of serum glypican-3 in the diagnosis of hepatocellular carcinoma by random-effects models. Summary receiver operating characteristic curve (sROC) analysis was performed to summarize the overall test performance. RESULTS: The results showed that the pooled overall diagnostic sensitivity, specificity, and 95% confidence interval (CI) for serum glypican-3 in the diagnosis of hepatocellular carcinoma were 68% (56-79%) and 92% (82-96.0%), respectively. Besides, the summary diagnostic odds ratio and 95% CI for glypican-3 were 23.53 (8.57-64.63). In addition, the area under sROC and 95% CI was 0.87 (0.84-0.90). The major design deficiencies of included studies were differential verification bias, and a lack of clear exclusion and inclusion criteria. CONCLUSIONS: The results of this meta-analysis suggested that serum glypican-3 was acceptable as a moderate diagnostic marker in the diagnosis of hepatocellular carcinoma compared with healthy individuals, which could elevate the sensitivity and specificity of diagnosis. Furthermore, more well-designed studies with large sample sizes are needed to show the effectiveness of glypican-3 in the differential diagnosis of hepatocellular carcinoma.

[Preliminary study on mechanisms of granulocyte macrophage-colony stimulating factor in enhancing impaired colonic anastomotic healing in rats treated with intraperitoneal oxaliplatin].

OBJECTIVE: To investigate the mechanisms of local application of granulocyte macrophage-colony stimulating factor (GM-CSF) on healing of colonic anastomoses impaired by intraperitoneal oxaliplatin in rats. METHODS: Sixty 10-week-old male Wistar rats were made the colonic anastomosis model and randomized into 3 groups, 20 rats in each. The rats received intraperitoneal injection of 5% dextrose in group A, and intraperitoneal injection of 5% dextrose and 10 mL oxaliplatin (25 mg/kg) in group B at 1 day; and 50 microg GM-CSF was injected into the perianastomotic area immediately after operation and 10 mL intraperitoneal oxaliplatin (25 mg/kg) was given at 1 day. The general situation of rats was observed after operation. Anastomotic healing was tested by measuring the bursting pressure in vivo at 2, 3, 5, 7 days. Anastomotic healing score was evaluated by histological staining. Immunohistochemical staining of the anastomotic site was used to determine the amount of collagen type I content. RESULTS: All animals survived to the experiment end. There was no significant difference in the bursting pressure among 3 groups at 2 and 3 days (P > 0.05); the bursting pressure of group B was significantly lower than that of groups A and C (P < 0.05). There was no significant difference in mononuclear cells infiltration, mucosal epithelialization, submucosa-muscle layer connection degree, and granulation tissue formation between groups A and C at different time points (P > 0.05); groups A and C were significantly better than group B in mucosal epithelialization and granulation tissue formation (P < 0.05). Groups A and C were significantly better than group B in mononuclear cells infiltration at 2 and 3 days, and in submucosa-muscle layer connection degree at 5 and 7 days (P < 0.05). There was no significant difference in collagen type I content among 3 groups at 2 and 3 days (P > 0.05); the content of collagen type I in groups A and C were significantly higher than that in group B (P < 0.05) at 5 and 7 days. CONCLUSION: Local administration of GM-CSF may enhance colonic anastomotic healing by early stimulating infiltration of macrophages and increasing collagen deposition.