[Expression of CD90/EpCAM/CD24 in hepatocellular carcinoma cell lines at various stages of differentiation].

OBJECTIVE: To confirm the malignant phenotype of hepatocarcinoma cell (HCC) lines at various stages of differentiation (MHCC97L, MHCC97H and HCCLM3) and to explore their expression levels of cancer stem cell (CSC) markers. METHODS: The invasive and proliferative properties of each HCC line were assessed by transwell assay and the Cell Counting Kit-8 (CCK-8) colorimetric assay. Sensitivity to chemotherapy was assessed by treatment with oxaliplatin and determination of the half inhibitory concentration (IC50). The expression of CD90, EpCAM and CD24 was measured by flow cytometry. RESULTS: The number of cells that migrated through the invasion assay membrane were significantly different between the three HCC lines: HCCLM3 (30.57 +/- 8.95) more than MHCC97H (21.33 +/- 4.17) more than HCC97L (9.33 +/- 3.85), P less than 0.01. The IC50 was significantly different between the three HCC lines: HCCLM3 (36.57 +/- 6.95) mumol/L more than MHCC97H (26.35+/-3.88) mumol/L more than MHCC97L (17.68 +/- 3.25) mumol/L. The CSC marker with the highest expression on all three HCC lines was CD90 (HCCLM3: 0.92% +/- 0.21%, MHCC97H: 1.98% +/- 0.23%, and MHCC97L: 2.55% +/- 0.34%), followed by EpCAM (2.11% +/- 0.32%, 3.23% +/- 0.18%, and 4.38% +/-0.49%, respectively), and CD24 as the lowest (0.68% +/- 0.37%, 1.22% +/- 0.26%, and 1.36% +/- 0.24%, respectively). CONCLUSION: Higher expression of CSC markers on HCC lines is associated with a stronger invasive ability and higher sensitivity to chemotherapy.

Alpha-fetoprotein: the predictor of microvascular invasion in solitary small hepatocellular carcinoma and criterion for anatomic or non-anatomic hepatic resection.

BACKGROUND/AIMS: This study aimed to identify the preoperative predictors of microvascular invasion (MVI) in solitary small hepatocellular carcinoma (HCC) and evaluate their application in surgical treatment. METHODOLOGY: We retrospectively analyzed 161 patients with solitary small HCC who underwent curative hepatic resection. Overall and disease-free survival rates were calculated by Kaplan-Meier method and compared by log-rank test. The independent predictors were identified by Cox proportional hazards model. RESULTS: MVI was an independent predictor of both overall and disease-free survival. In 51 patients with MVI, anatomic resection achieved better survival than non-anatomic resection. However, anatomic resection and non-anatomic resection brought similar survival in patients without MVI. Alpha-fetoprotein (AFP) was identified as the unique predictor of MVI (HR=2.773, p=0.004). Anatomic resection achieved better survival outcome than non-anatomic resection when AFP >100µg/L (5-year overall survival rate: 85% vs. 55%, p=0.024; 5-year disease-free survival rate: 37% vs. 21%, p=0.025), while there was no statistical survival difference between anatomic and non-anatomic resection when AFP <=100µg/L (5-year overall survival rate: 85% vs. 76%, p=0.838; 5-year disease-free survival rate: 48% vs. 49%, p=0.921). CONCLUSIONS: Compared with non-anatomic resection, anatomic hepatic resection improves overall and disease-free survival of solitary small HCC patients with AFP >100µg/L.

Preoperative predictors of short-term survival after hepatectomy for multinodular hepatocellular carcinoma.

AIM: To investigate preoperative factors associated with poor short-term outcome after resection for multinodular hepatocellular carcinoma (HCC) and to assess the contraindication of patients for surgery. METHODS: We retrospectively analyzed 162 multinodular HCC patients with Child-Pugh A liver function who underwent surgical resection. The prognostic significance of preoperative factors was investigated by univariate analysis using the log-rank test and by multivariate analysis using the Cox proportional hazards model. Each independent risk factor was then assigned points to construct a scoring model to evaluate the indication for surgical intervention. A receiver operating characteristics (ROC) curve was constructed to assess the predictive ability of this system. RESULTS: The median overall survival was 38.3 mo (range: 3-80 mo), while the median disease-free survival was 18.6 mo (range: 1-79 mo). The 1-year mortality was 14%. Independent prognostic risk factors of 1-year death included prealbumin < 170 mg/L [hazard ratio (HR): 5.531, P < 0.001], alkaline phosphatase > 129 U/L (HR: 3.252, P = 0.005), α fetoprotein > 20 µg/L (HR: 7.477, P = 0.011), total tumor size > 8 cm (HR: 10.543; P < 0.001), platelet count < 100 × 109/L (HR: 9.937, P < 0.001), and γ-glutamyl transpeptidase > 64 U/L (HR: 3.791, P < 0.001). The scoring model had a strong ability to predict 1-year survival (area under ROC: 0.925, P < 0.001). Patients with a score ≥ 5 had significantly poorer short-term outcome than those with a score < 5 (1-year mortality: 62% vs 5%, P < 0.001; 1-year recurrence rate: 86% vs 33%, P < 0.001). Patients with score ≥ 5 had greater possibility of microvascular invasion (P < 0.001), poor tumor differentiation (P = 0.003), liver cirrhosis with small nodules (P < 0.001), and intraoperative blood transfusion (P = 0.010). CONCLUSION: A composite preoperative scoring model can be used as an indication of prognosis of HCC patients after surgical resection. Resection should be considered with caution in patients with a score ≥ 5, which indicates a contraindication for surgery.