Progress in the molecular mechanism and the prediction of postoperative recurrence of hepatocellular carcinoma / 中国实用外科杂志

The radical resection is the most important treatment for primary liver cancer, but the high recurrence rate is the main obstacle to the survival of postoperative patients.According to the time of tumor recurrence, the postoperative recurrence of liver cancer is divided into the early recurrence and late recurrence. The former is mainly related to the invasion and metastasis of liver cancer, and the latter is mainly caused by multicenter tumor occurrence based on the background of liver disease. The early prediction of postoperative recurrence risk contributes to the timely and effective intervention and improved the prognosis of the patients. In the past ten years, the clinical research on the recurrence of liver cancer has been systematically studied. The molecular mechanism of the metastasis and recurrence has been newly recognized: the metastatic potential of liver cancer begins in the early stage of primary tumor; the imbalance of micro-environmental inflammatory response promotes the metastasis of cancer. At the same time, a variety of molecular markers for predicting the recurrence of liver cancer were identified, and a molecular prediction model for the metastasis of liver cancer was created and optimized. These research results lay the foundation for more accurately understanding of the recurrence and metastasis of liver cancer and developing the more precise prevention and treatment strategies.

High expression of thrombin receptor PAR1 in peritumoral liver tissue is associated with poor survival after curative resection of hepatocellular carcinoma in early stage / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To evaluate the relationship between PAR1 (Protease-Activated Receptor 1) expression and the clinicopathologic features and to investigate the prognostic value of PAR1 expression in hepatocellular carcinoma (HCC) in early stage after curative resection.</p><p><b>METHODS</b>Real-time PCR was used to detect PAR1 expression in 41 pairs of tumors and matched peritumoral samples of HCC in early stage. Prognostic value of PAR1 mRNA expression was evaluated. Meanwhile, another 49 tissue paraffin slices of HCC were tested using immunohistochemistry (Envision) and the prognostic value of PAR1 expression and other clinicopathologic factors were evaluated.</p><p><b>RESULTS</b>Peritumoral PAR1 mRNA expression was significantly increased in HCCs from the patients with tumor recurrence as compared with those without recurrence (P < 0.05). Peritumoral PAR1 protein expression was related to tumor differentiation (P < 0.05). Kaplan-Meier analysis showed that Peritumoral PAR1 protein expression was associated with the overall survival (OS) (P < 0.05) of HCC patients and the time to recurrence (TTR) (P < 0.05). The 1, 3 and 5 -year overall survival time and the cumulative recurrence time in the high PAR1 protein expression group were significantly lower as compared to the low PAR1 expression group in the peritumoral liver tissue.</p><p><b>CONCLUSIONS</b>Peritumoral PAR1 expression is closely associated with the prognosis of early stage HCC patients after curable surgery. PAR1 may be involved in thrombin-mediated invasion process and may be used as a prognostic marker for HCC.</p>

Identification of metastasis-related microRNAs of hepatocellular carcinoma in hepatocellular carcinoma cell lines by quantitative real time PCR / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To identify the metastasis-related miRNAs in hepatocellular carcinoma (HCC) cell lines.</p><p><b>METHODS</b>A qRT-PCR method was established and optimized.</p><p><b>RESULTS</b>All candidate metastasis associated miRNAs except miR-124a were expressed in high metastasis cell line MHCC97H and low metastasis cell line MHCC97L, while some miRNAs were differentially expressed between liver cancer cell line (HepG2) and hepatic cell line (L02) (P less than 0.05), these miRNAs include: miR-148b (1.96+/-0.51 vs 3.76+/-0.28), miR-9 (-4.38+/-0.86 vs -1.10+/-0.53), miR-30c (8.41+/-0.40 vs 6.82+/-0.29), miR-338 (3.14+/-0.29 vs -2.36+/-0.32), miR-34a (0.71+/-0.40 vs -2.95+/-0.26), Let-7g (-4.07+/-0.55 vs -6.98+/-0.56). miR-148b expression was about 4 times higher than miR-148a [5.46 (IQR 4.25-6.67) vs 1.29 (IQR 0.94-1.64)] in all cell line tested (Z=-5.097, P=3x10(-7)).</p><p><b>CONCLUSION</b>This study may help to understand the biological significance of miRNAs in HCC metastasis.</p>

Application of alpha-fetoprotein in the diagnosis of hepatocellular carcinoma / 中国医学科学院学报

<p><b>OBJECTIVE</b>To evaluate the usefulness of serum alpha-fetoprotein (AFP) in clinical diagnosis and screening for hepatocellular carcinoma (HCC).</p><p><b>METHODS</b>Totally 290 HCC patients, 48 liver cirrhosis patients, and 49 healthy subjects were enrolled in this study. Serum AFP analysis was performed to investigate the correlation between the serum AFP level in HCC and the clinical or biochemical parameters of the disease, which included the size and number of tumor and the TNM stage. Sensitivities and specificities of AFP in HCC prediction at different cut-off levels were determined.</p><p><b>RESULTS</b>The serum AFP level was significantly higher in HCC patients than in liver cirrhosis patients (P = 0.0274) and healthy subjects (P = 0.0001). Among 290 HCC patients, 95 patients (32.8%) were AFP-negative (AFP < 20 microg/L), 195 (67.2%) were AFP-positive (AFP > or =20 microg/L). Sensitivity and specificity of AFP at 20 microg/L cut-off was 67.2% and 29.2%, respectively, and the positive and negative predictive value was 85.2% and 12.8%, respectively. Sensitivity of AFP at 400 microg/L cut-off was only 42.8%. Serum AFP levels were significantly different among HCC with different tumor size (P = 0.0009), tumor number (P = 0.0001), and TNM stage [TNM I vs. TNM III-IV (P = 0.0001); TNM II vs. TNM III-IV (P = 0.0003)].</p><p><b>CONCLUSIONS</b>Increased serum AFP level is highly suggestive in HCC diagnosis. Combined with other imaging examinations, AFP level can be used for the screening of high risk population and for the follow-up of AFP-positive patients.</p>