Primary Hepatocellular Carcinoma Group Research Articles

A Co-Expression Network Reveals the Potential Regulatory Mechanism of lncRNAs in Relapsed Hepatocellular Carcinoma

BackgroundThe mechanistic basis for relapsed hepatocellular carcinoma (HCC) remains poorly understood. Recent research has highlighted the important roles of long non-coding RNAs (lncRNAs) in HCC. However, there are only a few studies on the association between lncRNAs and HCC relapse.MethodsDifferentially expressed lncRNAs and mRNAs between a primary HCC group and relapsed HCC group were identified using the edge R package to analyze the GSE101432 dataset. The differentially expressed lncRNAs and mRNAs were used to construct a lncRNA–mRNA co-expression network. Weighted gene co-expression network analysis followed by Gene Ontology (GO) enrichment analyses were conducted on the database. Furthermore, correlation and survival analyses were performed using The Cancer Genome Atlas database, and expression in the clinical samples was verified by qRT-PCR. Thereafter, we inputted the genes from the two groups into the HCC TNM stage and tumor grade database from TCGA. Finally, we performed Kaplan–Meier survival analysis on the lncRNAs related to relapsed HCC.ResultsIn this study, lncRNAs and mRNAs associated with HCC relapse were identified. Two gene modules were found to be closely linked to this. The GO terms in the yellow and black modules were related to cell proliferation, differentiation, and survival, as well as some transcription-related biological processes. Through qRT-PCR, we found that the expression levels of LINC00941 and LINC00668 in relapsed HCC were higher than those in primary HCC. Further, mRNA levels of LOX, OTX1, MICB, NDUFA4L2, BAIAP2L2, and KCTD17 were changed in relapsed HCC compared to levels in primary HCC. In addition, we verified that these genes could predict the overall survival and recurrence-free survival of HCC. Moreover, we found that LINC00668 and LINC00941 could affect tumor grade and TNM stages. In total, we identified and validated two lncRNAs (LINC00941 and LINC00668) and six mRNAs (LOX, MICB, OTX1, BAIAP2L2, KCTD17, NDUFA4L2) associated with HCC relapse.ConclusionIn summary, we identified the key gene modules and central genes associated with relapsed HCC and constructed lncRNA–mRNA networks related to this. These genes are likely to have potential prognostic value for relapsed HCC and might shed new light on novel biomarkers or diagnostic targets for relapsed HCC.

Value of ultrasound combined with MRI in the diagnosis of primary and recurrent hepatocellular carcinoma.

Ultrasound (US) combined with magnetic resonance imaging (MRI) in the diagnosis of primary hepatocellular carcinoma (PHCC) and recurrent hepatocellular carcinoma (RHCC) were compared. The clinical data of 329 patients with hepatocellular carcinoma (HCC) admitted to Qingdao Women and Children's Hospital from June 2015 to December 2017 were collected. One hundred and sixty patients with PHCC were regarded as the PHCC group, and the other 169 patients with RHCC were regarded as the RHCC group. US and MRI were used in the imaging diagnosis of both groups and the results of US combined with MRI, US, and MRI alone were compared. The lesion size in the PHCC group was significantly higher than that in the RHCC group (P<0.05). The MRI fast-in and fast-out rates of the two groups were significantly higher than those of the other three methods (P<0.05). The coincidence rate of MRI in the two groups was higher than that of computed tomography (CT), US, and US combined with MRI (P<0.05). The coincidence rates of CT, US, MRI, and US combined with MRI in PHCC group were significantly higher than those in RHCC group. In PHCC group, MRI was superior to the other methods in the detection of micro HCC (P<0.05). In RHCC group, MRI was significantly better than US in the detection of micro HCC (P<0.05). The sensitivity, specificity, positive predictive value and negative predictive value of MRI were significantly better than the other three methods (P<0.05). MRI alone has the best diagnostic efficacy for micro HCC-type lesions. The diagnostic efficacy of MRI, US, CT, and US combined with MRI in PHCC was better than those in RHCC. In addition to imaging examination, the diagnosis of RHCC should be combined with other indicators for comprehensive diagnosis.

Expression of three common serum enzymes in patients with hepatitis B related hepatocellular carcinoma

Objective To explore the clinical value of alanine aminotransferase(ALT), aspartate aminotransferase(AST) and gamma-glutamine transpeptidase(GGT) in the diagnosis of hepatitis B-related hepatocellular carcinoma, and to provide reference for clinical diagnosis. Methods From November 2015 to November 2017, 118 patients with hepatitis B-related primary liver cancer (hepatitis B-related primary liver cancer group) admitted to Tongji Huangzhou Hospital of Huazhong University of Science and Technology were selected.And 116 patients with cirrhosis (hepatocirrhosis group) and 114 healthy people were selected as control group.The levels of ALT, AST and GGT and the specificity and sensitivity of each index were compared among the three groups, and the ROC curve was analyzed. Results The levels of serum ALT, AST and GGT in the hepatitis B-related primary hepatocellular carcinoma group were higher than those in the cirrhosis group and the control group, and the above serum indicators in the cirrhosis group were higher than those in the control group[(267.1±131.5)U/L vs.(31.2±11.3)U/L vs.(17.4±4.6)U/L, (76.6±23.2)U/L vs.(45.2±13.1)U/L vs.(24.3±6.6)U/L, (125.3±42.6)U/L vs.(53.1±17.6)U/L vs.(22.4±4.4)U/L, all P<0.05]. ROC curve showed that the area under GGT curve was 0.85, under ALT curve was 0.78, and under AST curve was 0.73, the area under the combined diagnostic curve of the three indicators was 0.95.The sensitivity and specificity of three combined diagnosis were higher than those of ALT, AST and GGT. Conclusion The levels of serum ALT, AST and GGT in patients with hepatitis B-related primary liver cancer are elevated, and the combined diagnosis of the three indicators has high sensitivity and specificity, which is worthy of clinical reference. Key words: Liver neoplasms; Hepatitis B virus; Alanine transaminase; Aspartate kinase; γ-Glutamyltransferase; Serological indicators; ROC curve; Sensitivity; Specificity

Expression and clinical significance of CXC chemokine receptors 1 and 2 and CXCL8 in primary hepatocellular carcinoma

Objective To investigate the expression and clinical significance of CXC chemokine receptors 1 and 2 (CXCR1 and CXCR2) and CXCL8 in peripheral blood mononuclear cells (PBMCs) and liver biopsy tissues from patients with primary hepatocellular carcinoma (PHC). Methods Serum specimens were collected from 36 patients with PHC, 30 patients with liver cirrhosis and 28 healthy subjects. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to measure the expression of CXCR1, CXCR2 and CXCL8 at mRNA level in PBMCs. Streptavidin-perosidase (SP) immunohistochemistry was used to detect the expression of CXCR1, CXCR2 and CXCL8 at protein level in liver biopsy tissues. Levels of C-reactive protein (CRP), alpha-fetoprotein (AFP) and ferritin (FER) in the serum specimens were detected by chemiluminescence immunoassay. Then the correlations between these markers were analyzed. Results All of the results showed that the expression of CXCR1, CXCR2 and CXCL8 at mRNA level in PBMCs from the PHC group were higher than those of the healthy control group (P<0.01) as well as those of the liver cirrhosis group (P<0.05). Up-regulated expression of CXCR1, CXCR2 and CXCL8 in patients with PHC were associated with the depth of tumor invasion, lymph node or distant metastasis, clinical stage and levels of CRP, AFP and FER in serum (P<0.05). The expression of CXCR1, CXCR2 and CXCL8 at protein level in liver biopsy tissues were also significantly increased in the PHC group in comparison with those of the healthy control group as indicated by the result of SP immunohistochemistry (P<0.05). Conclusion Levels of CXCR1, CXCR2 and CXCL8 in the patients with PHC are significantly increased and positively correlated with the levels of AFP, FER and CRP in serum, suggesting that the signal transduction process mediated by CXCR1, CXCR2 and their common ligand CXCL8 may play a key role in the pathological process of PHC. This study may provide a potential new strategy for immune intervention in hepatocellular cancer. Key words: PHC; CXCR1; CXCR2; CXCL8; mRNA; AFP; FER; CRP

A Systematic Review of Des-γ-Carboxy Prothrombin for the Diagnosis of Primary Hepatocellular Carcinoma.

Determining the serum des-γ-carboxy-prothrombin (DCP) level is of great importance for the diagnosis of primary hepatocellular carcinoma (PHC). Although several studies have investigated the accuracy of diagnostic DCP tests for PHC, the results have been inconsistent.The aim of this study was to systematically evaluate DCP as a diagnostic standard for PHC.Several databases, including PubMed, EMBASE, MEDLINE (Ovid), the Chinese National Knowledge Infrastructure (CNKI), the VIP Database for Chinese Technical Periodicals (VIP), WanFang Data, and the China Biological Medicine Database (CBM), were searched from the date of database inception until July 1, 2015 to collect published international and domestic studies of DCP in the diagnosis of PHC. Two investigators screened the literature according to the inclusion and exclusion criteria, extracted the data, and assessed the methodological quality of the included studies.A total of 38 studies involving 11,124 cases were included (5298 cases in the PHC group and 5826 cases in the control group). A meta-analysis was then performed using Meta-Disc 1.4 and RevMan 5.2 software. The overall sensitivity, specificity, positive likelihood ratio (+LR), and negative likelihood ratio (−LR) of DCP for the detection of PHC were 0.66 (95% confidence interval [CI]: 0.65–0.68), 0.88 (95% CI: 0.87–0.90), 7.13 (95% CI: 5.73–8.87), and 0.33 (95% CI: 0.29–0.38), respectively. The area under the curve (AUC) of the summary receiver-operating characteristic curve (SROC) was 0.9002. In conclusion, DCP has moderate diagnostic utility for PHC. Owing to the heterogeneity and limitations of the included studies, the above conclusion requires further support from additional high-quality studies.

Gene copy number, mRNA transcription and protein expression of PD-1 gene in primary hepatocarcinoma patients

To study the gene copy number, mRNA transcription and protien expression of programmed cell death 1 (PD-1) gene in primary hepatocellular carcinoma (PHC) patients and normal control individuals (NC) who are anti-HBs positive, and to investigate the variations in PD-1 gene copy numbers and its relationship with PHC. Real-time PCR was adopted to detect the PD-1 gene copy numbers and their mRNA expressions in peripheral blood mononuclear cells (PBMCs) from 24 samples of PHC patients and 26 of NC. Protein expression level of PD-1 on CD8+ T was analyzed by flow cytometry. In terms of number of PD-1 gene copy numbers, the percentage of cases of haploid (single) was 34.62% and 4.17% in PHC group and control group respectively while the percentage of cases of diploid (double) was 61.54% and 95.83% respectively. The difference between the two was statistically significant (chi2 = 7.639, P = 0.006). The rate of cases with double PD-1 gene copy numbers was found to be higher in patients with PHC than in control group. It was also found that the average expression of PD-1 mRNA was 2.35E-03 in control group and 1.23E-03 in PHC group. The expression level was significant lower in PHC group than that in control group when compared by using Mann-whitey technic (U = 153, P = 0.009). Furthermore, the frequency of PD-1 protein expression on CD8+ T cells was 3.72 +/- 0.32 in control group and 16.13 +/- 1.68 in PHC group. The level of PD-1 mRNA expression was higher in PHC and significant differences was shown between two groups (t = -7.073, P = 0.000). Our study suggests that the variation in PD-1 gene copy number may trigger primary hepatocellular carcinoma to HBV carriers. The relationship between the variation of PD-1 gene copy numbers and its association with primary hepatocellular carcinoma is worth further focus.

Radiofrequency ablation of recurrent hepatocellular carcinoma after hepatectomy

To assess the efficiency and safety of radiofrequency ablation (RFA) of recurrent hepatocellular carcinoma (RHCC) after hepatectomy and to investigate efficacy of RFA for patients with early and late phase recurrence, separately, setting 1 year as the cut-off between the early and late phases. A total of 42 patients with 77 RHCC and a history of hepatic resection for hepatocellular carcinoma (HCC) underwent ultrasound-guided percutaneous radiofrequency ablation in our department and entered this study (RHCC group). The average diameter of RHCC was (3.8 +/- 1.4) cm (range, 1.5-6.6 cm). 21 of the 42 RHCC patients had Child-Pugh class A cirrhosis 19, class B and two, class C cirrhosis. The average interval between initial surgery and the diagnosis of recurrence was 22.8 months (range, 1-96 month). 42 RHCC patients were divided into two groups as early recurrence group including 20 patients with 40 RHCC, and late recurrence group including the other 22 patients with 37 RHCC according to the recurrence interval. During the same period 148 patients with 217 primary HCC were also treated by RF ablation and regarded as primary HCC group. The average diameter of primary HCC was (4.0 +/- 1.4) cm (range, 1.2-7.0 cm). Regular follow-up with enhanced CT was performed to evaluate the treatment results. Ablation was considered a success if no contrast enhancement was detected in the treated area on 1 month CT scans. The ablation success rate, local recurrence rate, new tumor incidence and mean survival in RHCC group were 90.5%, 14.3%, 38.1% and (28.0 +/- 3.5) months, respectively, which were similar to the corresponding results of 87.2%, 16.2%, 37.8% and (39.0 +/- 2.1) month in primary HCC group. However, when further comparison was performed between early recurrence group, late recurrence group and primary HCC group, there were some significant differences. The incidence of new tumors in early recurrence group was significantly higher than that in late recurrent group (60.0% vs. 18.2%, P = 0.005); early recurrence group survived shorter than primary HCC group [(15.4 +/- 2.3) vs. (39.0 +/- 2.1) months, P < 0.005]. The survival time was similar between late recurrence group and primary HCC group. One case was found haemorrhage after RFA and recovered with conservative treatment. No major complications occurred in the remaining 41 patients. RF ablation is generally effective and safe in treating RHCC. And it's more effective in late recurrence than in early recurrence.