In recent years, the diagnosis and treatment of hepatocellular carcinoma (HCC) has entered a brand-new era due to the advancement of diagnosis methods and the emergence of targeted drugs and immunotherapy drugs. The author described and summarized in detail the screening program, diagnostic thought and procedure, clinical staging, mechanism of targeted and immune therapy and application range of HCC.
Objective To explore the effects of DNA cross-linking repair 1B (DCLRE1B) gene on the migration and invasion ability of hepatocellular carcinoma cell. Methods Bioinformatics analysis was used to analyze the expression of DCLRE1B mRNA in hepatocellular carcinoma, and its relationship with the prognosis and related influencing factors of patients. Immunohistochemical staining was used to detect the expression of DCLRE1B protein in resected hepatocellular carcinoma tissues and their corresponding normal liver tissues. The DCLRE1B gene silenced Huh7 and HepG2 hepatocellular carcinoma cell lines were constructed by lentivirus, and the transfected effect was detected by Western blot. The migration and invasion of DCLRE1B silenced hepatocellular carcinoma cells were detected by scratch test and Transwell method. The changes of genes related to epithelial mesenchymal transformation (EMT) after DCLRE1B silencing were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Results ① The biological information analysis results showed that: The mRNA expression of DCLRE1B was highly expressed in a variety of tumors including hepatocellular carcinoma (P<0.05). The mRNA expression of DCLRE1B was associated with the TNM staging of tumor (P<0.05). The relative expression level of DCLRE1B mRNA in hepatocellular carcinoma patients was related to their prognosis. The overall survival situation (P=0.038) and progression free survival situation (P=0.005) of hepatocellular carcinoma patients in the high expression group were worse than those in the low expression group. Univariate and multivariate Cox analysis showed that the expression of DCLRE1B gene was an independent factor affecting the prognosis of hepatocellular carcinoma (P<0.05). ② The positive rate of DCLRE1B protein expression in resected hepatocellular carcinoma tissues was higher than that in normal liver tissues (P<0.05). ③ Cell experiment results showed that: After stable silencing DCLRE1B gene of hepatocellular carcinoma cell (Huh7 and HepG2) constructed by lentivirus, the expression of DCLRE1B protein was significantly down regulated (P<0.05). After silencing DCLRE1B gene, the migration and invasion ability of hepatocellular carcinoma cells were significantly decreased (P<0.05). After silencing DCLRE1B, the mRNA expressions of E-cadherin, matrix metalloproteinase 9, and β-catenin were up regulated (P<0.05), and the mRNA expressions of N-cadherin and Vimentin were down regulated (P<0.05), but the mRNA expression of zinc finger transcription factor had no significant change, and the difference was not statistically significant (P＞0.05). Conclusion Silencing DCLRE1B gene can inhibit the migration and invasion ability of hepatocellular carcinoma cells, and its mechanism may be related to the process of EMT.
We have devised a highly sensitive, specific, and quantitative assay for multidrug resistance (mdr1) mRNA expression based on the reverse transcription-polymerase chain reaction (RT-PCR). mdr1 mRNA levels were detected in 30 human primary hepatocellular carcinoma (PHC) tissue and adjacent liver tissue. Five of the patients had received chemotherapy before hepatectomy. The results show that the level of expression of mdr1 gene is higher in tumor tissue than in adjacent liver tissue. mdr1 gene is overexpressed in PHC after chemotherapy. Furthermore, mdr1 gene expression in the treated tumor adjacent liver tissue is higher than that in untreated tumor adjacent liver tissue. Our results indicated that overexpression of mdr1 gene may be responsible for the intrinsic and acquired drug resistance of PHC.
Objective To explore the expression and function of NDRG2 gene in human primary hepatocellular carcinoma and normal hepatic tissues. Methods The immunohistochemical ABC method， Western blot， and Real-time PCR were used to investigate the expression and content of NDRG2 in human hepatocellular carcinoma and hepatic normal biopsies. Results The NDRG2 protein located in cytoplasm. The positive rate was 16.67%（5/30） and 100%（30/30） in hepatocellular carcinoma and normal hepatic tissues, respectively. The relative content of NDRG2 protein in hepatocellular carcinoma and normal hepatic tissues were 0.029 0±0.005 9 and 0.109 2±0.002 8. There were significant differences between human hepatocellular carcinoma and hepatic normal biopsies both in staining positive rates and relative content（P＜0.05）. The Western blot also agreed with the result，the expression level of NDRG2 protein in hepatocellular carcinoma and normal hepatic tissues was 1.13±0.15 and 1.57±0.18， respectively, there was significant difference（P＜0.05）. Also, compared with normal hepatic tissues, the expression level of NDRG2 mRNA in carcinoma tissues was reduced significantly (0.89±0.15 vs. 1.48±0.17, P＜0.05). However, there were no significant differences in NDRG2mRNA expression between Edmondson-Steiner grades. Conclusions There possibly have difference in NDRG2 expression between human primary hepatocellular carcinoma and normal hepatic tissue. NDRG2 gene may take part in the pathogenesis of human primary hepatocellular carcinoma. Futher study will be needed to study its mechanism and function.
Objective To investigate immunological therapeutic effect and safety of dendritic cells (DCs) combined with heat shock protein 70 (HSP70)-peptide complex (PC) derived from autogeneic hepatoma tissue. Methods Thirty patients with hepatocellular carcinoma from February 2010 to February 2015 in the Gaochun People’s Hospital of Nanjing and The Third Affiliated Hospital of Nantong University were studied, and subsequently were divided into an immunotherapy group (treated with HSP70-PC/DCs vaccine,n=15) and a chemotherapy group (n=15) according to the prescribed postoperative treatment methods. The levels of T lymphocyte subtypes were assayed by FACS. The toxicity adverse reactions, alpha-fetoprotein (AFP), CA19-9, hepatic tumor recurrence rate, survival rate, and KPS of two groups patients were evaluated and compared between these two groups. Results ① The values of CD3+, CD4+, CD4+/CD8+, and CD3CD56 had no significant differences between the immunotherapy group and the chemotherapy group before treatment (P>0.05), which in the immunotherapy group were significantly higher than those in the chemotherapy group after treatment (P<0.05), and which were significantly higher in the immunotherapy group after treatment as compared with the levels before treatment (P<0.05), and which had no significant differences in the chemotherapy group between after treatment and before treatment (P>0.05). ② Before treatment, the levels of AFP and CA19-9 had no significant differences between the immunotherapy group and the chemotherapy group (P>0.05), which in the immunotherapy group were significantly lower than those in the chemotherapy group after treatment (P<0.05). In the immunotherapy group, the levels of AFP and CA19-9 after treatment were significantly lower than those before treatment (t=2.564，P=0.021；t=2.011，P=0.041), which in the chemotherapy group before treatment were decreased as compared with the levels before treatment (t=2.221,P=0.036;t=2.487,P=0.066). ③ The patients treated with the HSP-PC/DCs vaccines was well tolerated and no obvious toxicity was appeared. ④ All the patients were followed up 5–19 months with median follow-up time of 9 months. The median survival time was 560 d and 436 d in the immunotherapy group and the chemotherapy group, respectively. After treatment, KPS score was significantly higher and recurrence rate was significantly lower in the immunotherapy group as compared with the chemotherapy group (P<0.05). The total survival had no significant difference between the immunotherapy group and the chemotherapy group (P>0.05). Conclusions The preliminary results of limited cases in this study show that HSP70-PC/DC vaccination is safe and effective in treatment of hepatocellular carcinoma, the pulsed DCs are effective in activating specific T-cell responses against hepatocellular carcinoma cells. HSP70-PC/DC vaccine might improve immunity and prevent postoperative recurrence of hepatocellular carcinoma.
ObjectiveTo explore the combined application of neutrophil to lymphocyte ratio (NLR) and systemic immune inflammation index (SII) on the prognosis of hepatitis B-related hepatocellular carcinoma after resection.MethodsRetrospectively collected data of 180 patients with hepatitis B-related hepatocellular carcinoma who were hospitalized in the Department of Infectious Diseases and Hepatobiliary Surgery of the Affiliated Hospital of Southwest Medical University and received surgical treatment from January 2013 to December 2019, including general information, laboratory examination and abdominal CT or MRI results. NLR and SII values were measured at one week before operation, and their critical values of NLR and SII were determined by ROC curve analysis. Univariate and multivariate analysis were performed to determine the risk factors to predict the survival status of patients with hepatitis B-related hepatocellular carcinoma after hepatectomy.ResultsUnivariate analysis showed that AFP, platelets, TNM staging, portal vein tumor thrombus, tumor differentiation, NLR, SII, and NLR+SII combined score were significantly correlated with the prognosis of patients with hepatitis B-related hepatocellular carcinoma (P<0.05). Multivariate analysis showed that PLT [HR=1.791, 95%CI (1.124, 2.854), P=0.014], NLR [HR=4.289, 95%CI (2.571, 7.156), P<0.001], SII [HR=5.317, 95%CI (3.016, 9.374), P<0.001], and NLR+SII combined score [HR=7.901, 95%CI (4.124, 15.138), P<0.001] were independently correlated with the survival of patients with hepatitis B-related hepatocellular carcinoma.ConclusionsThe preoperative NLR+SII combined score can be used to evaluate the postoperative prognosis of patients with hepatitis B-related hepatocellular carcinoma. The higher the score, the lower the postoperative survival rate.
ObjectiveTo investigate the expression and clinical significance of cytochromes b561 (CYB561) in hepatocellular carcinoma (HCC). MethodsThe expression of CYB561 mRNA in HCC tissues and its relationship with prognosis were analyzed by database data. Immunohistochemistry (IHC) was used to detect the expression of CYB561 protein in 61 matched HCC tissues and their adjacent tissues, and the relationship between CYB561 protein expression and clinicopathological features and prognosis of HCC was analyzed. Kaplan-Meier method was used to draw the survival curve and Cox proportional hazard regression model was used to analyze the correlation between the expression of CYB561 protein and the prognosis of HCC. ResultsThe analysis of database data showed that the relative expression of CYB561 mRNA in HCC tissues was higher than that in adjacent tissues (P<0.001). Compared with HCC patients with negative expression of CYB561 mRNA, HCC patients with positive expression of CYB561 mRNA had worse overall survival (OS), relapse-free survival, progression-free survival and disease-free survival (all P<0.05). The results of IHC showed that the positive rates of CYB561 protein in HCC tissues and adjacent tissues were 57.38% (35/61) and 21.31%(13/61), respectively. The former was higher than the latter, with statistical significance (χ2=16.624, P<0.001). Survival analysis showed that the OS of patients with positive expression of CYB561 protein was worse than that of patients with negative expression (P<0.05). Multivariate Cox proportional hazard regression analysis showed that the positive expression of CYB561 protein was a risk factor for postoperative OS in HCC patients [HR=3.308, 95%CI (1.344, 8.144), P=0.009]. ConclusionCYB561 is positively expressed in HCC and suggests a worse survival, and may serve as a potential prognostic biomarker for HCC.
Objective To summarize the mechanism of microRNA in the recurrence and metastasis of hepatocellular carcinoma (HCC) and its possible clinical application. Methods The relevant literatures at home and abroad were reviewed to summarize the results of various scholars. Results microRNA played an important role in cell proliferation and apoptosis of HCC. microRNA of different types promoted or inhibited the recurrence and metastasis of HCC through different action targets and molecular pathways. Conclusions microRNA has a regulation role in the recurrence and metastasis of HCC, and the depth mechanisms study of microRNA in the recurrence and metastasis of HCC provides great significance to clinical therapy. The miRNA is expected to be one of the new target on the prediction and treatment of recurrence and metastasis in HCC.
ObjectiveTo understand the role of complement system in the immune mechanism of hepatocellular carcinoma (HCC) and its potential therapy value. MethodThe national and international literature relavant researches of complement system in the HCC was reviewed. ResultsBased on HCC as an immunogenic cancer and the complement system as a part of the innate immune system, it had potential application value in immunotherapy. Eight complement components (complement intrinsic components C1q, C3, and mannose binding lectin, soluble regulatory proteins complement factor H and C4b, and membrane regulatory proteins CD46 and CD59, as well as complement receptor C5aR1) were closely associated with HCC. The activation of the complement system could participate in the occurrence and development of HCC through various mechanisms. The complement inhibitor, it could regulate the activity of complement related activation pathways, enhance anti-tumor ability, and provide a potential new strategy for immunotherapy of HCC. ConclusionsAt present, only a few complement components have been found in HCC research. Although it has been found that multiple complement components play a role in regulating the immune mechanism of HCC, there is still no definite or recognized theoretical basis. In the future, further exploration of the protective or pathogenic mechanisms of complement components in HCC immunity is needed to objectively evaluate the risks and benefits of complement related inhibitor therapy and in combination with other anti-tumor immune therapies.
Primary liver cancer is the sixth most common malignancy and the third leading cause of cancer-related death worldwide, and hepatocellular carcinoma (HCC) constitutes the majority of primary liver cancer cases. The Liver Imaging Reporting and Data System (LI-RADS) was introduced to standardize the lexicon, acquisition, interpretation, reporting, and data collection of imaging results in patients at increased risk for HCC. LI-RADS allows effective categorization of focal liver lesions, and has been applied in the full clinical spectrum of HCC from diagnosis, biological behavior characterization, prognosis prediction, to treatment response assessment. This review aimed to summarize the recent applications of CT/MRI LI-RADS in the diagnosis, biological behavior characterization and prognosis prediction of HCC, discuss current challenges and shed light on potential future directions.