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.
ObjectiveTo investigate the expression of microRNA (miRNA, miR)-141-3p in hepatocellular carcinoma (HCC) tissues and its effect on proliferation and invasion of HCC.MethodsBioinformatics tools were used to predict putative miRs with search potential downstream gene–GP73, hsa-miR-141-3p was selected for further analysis and observations. A dual-luciferase reporter assay was performed to validate GP73 as a target of hsa-miR-141-3p. Real time PCR (qRT-PCR) or Western blot was performed to measure the expression level of miR-141-3p and GP73 in HCC and adjacent tissue. MTT, EdU, and Transwell were used to measure cell proliferation and migration.ResultsIt was identified that the expression level of miR-141-3p was significantly lower in the HCC tissues than that of adjacent tissues (P<0.05), but different in GP73 mRNA and its protein (P<0.05). Clinical analysis indicated that decreased miR-141-3p expression was significantly correlated with advanced tumor grade, advanced TNM stage, and vascular invasion (P<0.05). MTT assay showed that the absorbance (A) value of Huh-7 cells transfected with miR-141-3p overexpression plasmid was significantly decreased compared with the miR-negative control (NC) group (transfected empty plasmid) and the blank control group (P<0.05).The EdU detection results showed that the ratio of EdU positive cells in Huh-7 and MHCC-97H cells were lower than those in the blank control group and the miR-NC group after transfection of miR-141-3p (P<0.05). Transwell test found that after transfection of miR-141-3p, the number of invading cells and the number of migrated cells in MHCC-97H cells were lower than those in the blank control group and the miR-NC group (P<0.05). The results of cytological function recovery experiments showed that the number of invading cells and the number of migrated cells in MHCC-97H cells of miR-141-3p+GP73 group were lower than those in blank control group and miR-NC group (P<0.05), but higher than those of the miR-141-3p group and miR-141-3p+GP73-NC group (P<0.05).ConclusionsThe present study revealed that miR-141-3p is reduced in HCC tissues. Additionally, GP73 expression levels are negatively correlated to miR-141-3p in HCC tissues, and that is associated with the progression of HCC. Overexpression of miR-141-3p significantly inhibit proliferation, invasion, and migration of HCC cells.Reversal of partial inhibition of miR-141-3p can be achieved by restoring the expression of the GP73 gene without the 3′ untranslated region (UTR).
Objective To detect expression of miR-483-5p in surem of patients with hepatocellular carcinoma (HCC) and investigate it’s clinical significance for diagnosis of HCC. Methods The rerum samples of 112 patients with HCC (HCC group), 85 patients with chronic viral hepatitis B (CHB group), and 56 healthy people for physical examination (healthy control group) were collected from January 2010 to January 2012 in the First Hospital of Lanzhou University. According to the results of preliminary chip detection of miRCURY LNATM miRNA, the real-time fluorescent quantitative PCR was adopted to quantitate the serum levels of miR-483-5p and miR-500a and the routine electrochemical method was used to detect the serum alpha fetoprotein (AFP) in every group. The receiver operating characteristic (ROC) curve was utilized to analyze the diagnostic values of serum miR-483-5p, miR-500a, and AFP for the HCC. Results The serum levels of miR-483-5p and miR-500a in the HCC group were significantly higher than those of the CHB and healthy control groups (both P<0.000 1), which had no significant differences between the CHB group and the healthy control group (P>0.05). The serum miR-483-5p level of the HCC patient decreased markedly at the postoperative 30 d (P<0.000 1) as compared with the preoperative level. The area under the ROC curve (AUC) of miR-483-5p, miR-500a, AFP, or miR-483-5p in combination with AFP for the diagnosis of the HCC was 0.74 (cutoff value=2.842, sensitivity=74% and specificity=66%), 0.66 (cutoff value=1.830, sensitivity=74% and specificity=51%), 0.81 (cutoff value=20 μg/L, sensitivity=78% and specificity=70%), and 0.92 (cutoff value=3.78, sensitivity=81% and specificity=83%), respectively. The AUC values of miR-483-5p in the diagnosis of the HCC patients with positive AFP (AFP>20 μg/L) and negative AFP (0–20 μg/L) were 0.78 and 0.83, respectively. Conclusions Serum miR-483-5p highly expresses in HCC, which has a certain accuracy in diagnosis of HCC, it combined with AFP could further increase its diagnostic value. Serum miR-483-5p might play an important supplemental role in diagnosis of HCC patient with negative AFP.
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.
ObjectiveTo systematically review clinical value of des-γ-carboxy prothrombin (DCP) in the diagnostic of primary hepatocellular carcinoma (PHC).MethodsDatabases including PubMed, The Cochrane Library, EMbase, Medline (Ovid), CNKI, VIP, WanFang Data and CBM were electronically searched to collect relevant studies on DCP in the diagnosis of PHC from inception to December 31st, 2018. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies. Then, meta-analysis was performed by using Meta-Disc 1.4 software and RevMan 5.3 software.ResultsA total of 50 studies involving 15 099 cases were included. The results of meta-analysis showed that the pooled sensitivity, pooled specificity, pooled positive likelihood ratio, pooled negative likelihood ratio, pooled diagnostic odds ratio and area under the curve of SROC were 0.69 (95%CI 0.67 to 0.70), 0.89 (95%CI 0.89 to 0.90), 7.35 (95%CI 6.08 to 8.90), 0.31 (95%CI 0.27 to 0.35), 26.63 (95%CI 20.42 to 34.73) and 0.909 9, respectively.ConclusionsSerum DCP has higher diagnostic efficacy for PHC, especially with higher specificity of diagnosis. Due to the limited quality and quantity of included studies, the above results should be validated by more studies.
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 explore transcatheter arterial chemoembolization (TACE) influences on prognosis of patients with BCLC stage 0–A hepatocellular carcinoma (HCC).MethodsThe clinicopathologic data of BCLC stage 0–A HCC patients underwent the radical resection in the Affiliated Hospital of Southwest Medical University from January 2006 to June 2018 were retrospectively analyzed. These patients were divided into a preoperative TACE treatment group (PTT group, n=365) and a directly surgical resection group (DSR group, n=365). The Kplan-Meier method was used to compare the overall survival (OS) and disease free survival (DFS) between the two groups. The Cox proportional hazard model was used to analyze whether the preoperative TACE was an independent factor affecting the prognosis of patient with BCLC stage 0–A HCC.ResultsA total of 465 patients with BCLC stage 0–A HCC were enrolled, including 365 patients in the DSR group and 100 patients in the PTT group. The baseline data of the two groups were similar（P>0.050）. In the cohort, the 1-, 3-, 5-, 10-year OS rates and DFS rates were 95.3%, 83.5%, 74.3%, 56.8% and 88.0%, 63.8%, 51.1%, 36.4%, respectively in the DSR group, which were 92.7%, 72.9%, 52.3%, 35.3% and 78.1%, 54.2%, 40.4%, 31.2%, respectively in the PTT group. The Kplan-Meier survival analysis showed that the OS and DFS in the DSR group were significantly better than those in the PTT group (P=0.009, P=0.033). The multivariate Cox proportional hazard model analysis showed that the preoperative TACE was the independent risk factor for the poor prognosis in the patients with BCLC stage 0–A HCC [ HR=1.389, 95% CI (1.158, 2.199), P=0.021].ConclusionsFor patients with BCLC stage 0–A HCC, preoperative TACE doesn’t improve patient’s prognosis and might reduce survival rate. If there is no special reason, direct surgery should be performed.
ObjectiveTo investigate the expression change characteristic of stemness-related markers for recurrent hepatocellular carcinoma (HCC), and to discuss the relationship between stemness-related markers and clinicopathologic characteristics of HCC.MethodsWe collected 25 recurrent HCC patients who also had the first liver resection for HCC in Sichuan Cancer Hospital from Jan. 2010 to Oct. 2018. Immunohistochemistry was used to compare expressions of CD133, CD90, CD117, and epithelial cell adhesion molecule (EpCAM) in HCC tissues. Fluorescence in situ hybridization was used to detect telomere length.ResultsThe primary HCC had higher platelet count, larger tumor, less microvascular invasion (MVI), and less multiple HCC than the recurrent HCC (P<0.05), but the expressions of CD90, CD133, CD117, and EpCAM were not significantly differed after recurrence (P>0.05). The expressions of CD90, CD133, CD117, and EpCAM were not associated with tumor size, tumor number, Barcelona Clinic Liver Cancer Staging (BCLC staging), satellite nodules, and differentiation (P>0.05). The MVI-positive group had a significantly higher expression level of EpCAM (P=0.016) and longer telomere length (P=0.001). The telomere length was longer for tumors diameter less than 5 cm (P=0.038) and poor differentiation (P=0.046). Correlation analysis found that there was no relationship between telomere length and expression levels of EpCAM (r=–0.092, P=0.513), CD90 (r=–0.235, P=0.100), CD133 (r=0.024, P=0.867), and CD117 (r=–0.277, P=0.052), but an apparent positive correlation between expression levels of EpCAM and CD133 was found (r=0.358, P=0.011). Survival analysis found that poor differentiation (P=0.003) and BCLC B–C staging (P=0.040) were the risk factors of disease-free survival for patients after first HCC resection, and BCLC B–C staging (P=0.017) and tumor diameter more than 5 cm (P=0.035) were the risk factors for recurrent HCC.ConclusionsRecurrent HCC had similar stemness-related markers expression and longer telomere length. Expression level of EpCAM and telomere length were associated with MVI.
ObjectiveTo investigate the feasibility of associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) combined with mixed reality holographic imaging in treating the massive hepatocellular carcinoma.MethodThe clinicopathologic data of 1 patient with massive hepatocellular carcinoma underwent the ALPPS combined with mixed reality holographic imaging in the Guangdong Second Traditional Chinese Medicine Hospital on January 2019 were retrospectively analyzed.ResultsA 58-year-old female patient, the preoperative CT scan and enhanced scan of the abdomen revealed a 12.0 cm×10.5 cm×17.0 cm mass in the right lobe of the liver, with preoperative Child-Pugh grade A liver function. The ALPPS was performed after the preoperative evaluation. The associating liver partition and portal vein ligation was performed and the mixed reality holographic imaging was used during the stage Ⅰ operation. On day 21 after the stage Ⅰ operation, the CT results of the volume of left lateral lobe of liver was approximately 57.64%. On day 24 after the stage Ⅰ operation, the patient underwent the stage Ⅱ operation (radical hepatectomy). The patient received the chemotherapy after the operation. The courses of those operations were successful. And no severe complications occurred after the operation. The postoperative pathological results showed a moderately differentiated hepatocellular carcinoma with multiple foci and a maximum diameter of 13 cm. Six months after the last operation, there was no new intrahepatic metastasis and other metastases were found.ConclusionsALPPS combined with mixed reality holographic imaging is effective in treatment of massive hepatocellular carcinoma. Mixed reality holographic imaging could show anatomical details with three dimensions, it is beneficial for estimating future liver reserve before operation and locating during operation, and there is also a positive significance of postoperative recovery.
Objective To investigate relationship between hypoxia microenvironment and occurrence and development of hepatocellular carcinoma (HCC). Method The relevant literatures on researches of the relationship between the hypoxic microenvironment and the HCC were review and analyzed. Results The hypoxia microenvironment played an important role in inducing the drug resistance and angiogenesis of the HCC cells, and it was an important factor of affecting the ability of tumor metabolism, invasion, and migration. The hypoxia microenvironment could up-regulate the expression of hypoxia-inducible factors (HIFs) and promote its transcriptional activity, promote the expression of the vascular endothelial growth factor gene, and regulate the neovascularization in the tumor. Among them, the HIF-1α played a major role in regulating the angiogenesis, immune escape, tumor invasion and metastasis-related gene expression, participating in the glycolysis, regulating lysyl oxidase 2 and thus regulated epithelial-mesenchymal transition, then promoted the invasion and metastasis of the HCC; HIF-2α was a key regulator of the malignant phenotype involving in the cell proliferation, angiogenesis, apoptosis, metabolism, metastasis, and resistance to chemotherapy. The hypoxia microenvironment posed some difficulties for the treatment of HCC, but it was also a potential therapeutic breakthrough. Conclusion Hypoxia microenvironment can promote invasion and metastasis of HCC through various mechanisms, which provides new targets and strategies for clinical treatment of HCC.