ABSTRACT
BACKGROUND: Alpha-fetoprotein (AFP) is one of the diagnostic standards for primary liver cancer (PLC); however, AFP exhibits insufficient sensitivity and specificity for diagnosing PLC. AIM: To evaluate the effects of high-risk factors and the diagnostic value of AFP in stratified PLC. METHODS: In total, 289 PLC cases from 2013 to 2019 were selected for analysis. First, the contributions of high-risk factors in stratifying PLC were compared according to the following criteria: Child-Pugh score, clinical stage of liver cirrhosis, tumor size, and Barcelona Clinic Liver Cancer (BCLC) stage. Then, the diagnostic value of AFP was evaluated in different stratifications of PLC by receiver operating characteristic curves. For PLC cases in which AFP played little role, the diagnostic values of carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA 19-9), gamma-glutamyl transferase (GGT), and AFP were analyzed. RESULTS: The roles of high-risk factors differed in stratified PLC. The incidence of smoking and drinking history was higher in PLC with Child-Pugh scores of C (P < 0.0167). The hepatitis B virus (HBV) infection rate in PLC with cirrhosis was more than in PLC without cirrhosis (P < 0.0167). Small tumors were more prone to cirrhosis than large tumors (P < 0.005). BCLC stage D PLC was more likely to be associated with HBV infection and cirrhosis (P < 0.0083). AFP levels were higher in PLC with cirrhosis, diffuse tumors, and BCLC stage D disease. In diagnosing PLC defined as Child-Pugh A, B, and C, massive hepatoma, diffuse hepatoma, BCLC stage B, C, and D, and AFP showed significant diagnostic value [all area under the curve (AUC) > 0.700]. However, these measures were meaningless (AUC < 0.600) in small hepatomas and BCLC A stage PLC, but could be replaced by the combined detection of CEA, CA 19-9, GGT, and AFP (AUC = 0.810 and 0.846, respectively). CONCLUSION: Stratification of PLC was essential for precise diagnoses and benefited from evaluating AFP levels.
ABSTRACT
Liver cancer, which is the second leading cause of tumor-associated mortality, is of great concern worldwide due to its resistance to chemotherapeutic drugs. Transcatheter arterial chemoembolization (TACE) has previously been used as a treatment for unresectable liver tumors in China; however, the response to TACE treatment differs between patients. It has been reported that hepatitis B virus (HBV)-as sociated tumors are less sensitive to TACE treatment compared with non-HBV-associated liver cancer. Previous studies have demonstrated that exosomes serve a crucial role in hepatic carcinoma chemoresistance. We therefore hypothesized that HBV may modulate chemosensitivity via exosomes. The aim of the present study was to investigate how exosomes affect chemoresistance by assessing their role in chaperone-mediated autophagy (CMA)-dependent chemoresistance in HBV-associated liver cancer. Iconography data from HBV-positive and HBV-negative patients with hepatic carcinoma receiving TACE treatment were assessed, and it was revealed that the tumor volume was decreased in the patients with non-HBV-associated liver cancer compared with that in the patients with HBV-associated tumors following TACE therapy. Furthermore, it was revealed that exosomes from HBV-infected liver cancer cells were able to downregulate cell apoptosis when treated with oxaliplatin compared with exosomes from normal HepG2 cells. Furthermore, the results demonstrated that HBV-associated exosomes modulate cell death via activating the CMA pathway, and its key molecule, lysosome-associated membrane protein (Lamp2a), was also upregulated. Lamp2a-knockdown was also found to reverse anti-apoptotic effects in liver cancer. Taken together, the results of the present study suggest that chemoresistance in patients with HBV-associated hepatic tumors may be mediated by exosomes, and thus may provide a basis for the development of novel treatment strategies for chemoresistant liver cancer.
