OBJECTIVE: To identify the differentially expressed genes (DEGs) in peripheral blood mononuclear cells (PBMC) of patients with hepatocellular carcinoma (HCC) and to analyze their regulatory network. METHODS: The DEGs in PBMCs of HCC patients were screened based on GEO database. The functional enrichment analysis and interaction analysis were carried out for DEGs. MCODE algorithm was used to screen core genes of DEGs, and the mirDIP and starBase online tools were used to predict upstream miRNAs and lncRNAs of the core genes. RESULTS: A total of 265 DEGs with a high credibility were identified, which were mainly enriched in the biological activity, such as regulation of cell proliferation, metabolic regulation, cell communication and signaling, and inflammatory diseases according to Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, and the two analyses were correlated. Four diagnostic candidate genes were identified, including FUS RNA binding protein, C-X-C motif chemokine ligand 8, cullin 1 and RNA polymerase Ⅱ subunit H. Subsequently, 10 miRNAs, 1 lncRNAs and 38 circRNAs were predicted, and finally a lncRNA/circRNA-miRNA-mRNA-pathway regulatory networks was constructed. CONCLUSIONS The diagnostic candidate genes and its regulatory network in HCC PBMC have been identified based on data mining, which could provide potential tumor biomarkers for early diagnosis and treatment of HCC.
Carcinoma, Hepatocellular ; physiopathology ; Gene Expression Regulation, Neoplastic ; Gene Regulatory Networks ; Humans ; Leukocytes, Mononuclear ; metabolism ; Liver Neoplasms ; physiopathology

OBJECTIVETo investigate the risk factors of metachronous bone metastasis after radical resection of colorectal cancer within 5 years.

METHODSClinical data of 1 749 patients with colorectal cancer, of whom 50(2.8%) patients developed metastasis to bone after operation, in the Department of Colorectal Surgery, Changhai Hospital of The Second Military Medical University from January 2001 to December 2010 were analyzed retrospectively. Univariate and multivariate analysis were performed to find the risk factors of metachronous bone metastasis from colorectal cancer using Chi square test and Logistic regression, respectively.

RESULTSOf 50 colorectal cancer cases with bone metastasis, 29 were male and 21 were female. The age was ≥ 60 years old in 28 cases. Tumors of 36 cases were located in the rectum and of 14 cases located in the colon. Pathology examination showed 43 cases were adenocarcinomas, 7 cases were mucinous adenocarcinoma. Forty-two cases had T3-4 stage lesions, 30 cases had lymph node metastasis, 14 cases had pulmonary metastasis, and 5 cases had liver metastasis. Univariate Chi square test indicated that factors associated with the metachronous bone metastasis of colorectal cancer within 5 years were tumor site (χ=4.932, P=0.026), preoperative carbohydrate antigen 199 (CA199) level (χ=4.266, P=0.039), lymph node metastasis (χ=13.054, P=0.000) and pulmonary metastasis(χ=35.524, P=0.000). The incidence of bone metastasis in patients with rectal cancer (3.6%, 36/991) was higher compared to those with colon cancer (1.8%, 14/758). The incidence of bone metastasis in patients with higher(> 37 kU/L) preoperative serum CA199 level (4.9%, 12/245) was higher compared to those with lower serum CA199 level (2.5%, 38/1504). The incidence of bone metastasis in patients with lymph node metastasis(4.8%,30/627) and pulmonary metastasis (11.6%, 14/121) was significantly higher compared to those without lymph node metastasis (1.8%, 20/1122) and pulmonary metastasis(2.2%, 36/1628), respectively. Logistic multivariate analysis showed that rectal cancer(OR:0.508, 95%CI:0.268 to 0.963, P=0.038), lymph node metastasis (OR:2.291, 95%CI:1.273 to 4.122, P=0.006) and metachronous pulmonary metastasis(OR:4.796, 95%CI:2.473 to 9.301, P=0.000) were the independent risk factors of metachronous bone metastasis of colorectal cancer within 5 years.

CONCLUSIONPatients with rectal cancer, lymph node metastasis and metachronous pulmonary metastasis are high risk groups of metachronous bone metastasis after radical resection of colorectal cancer within 5 years.

Adenocarcinoma ; surgery ; Aged ; Biomarkers, Tumor ; blood ; Bone Neoplasms ; epidemiology ; secondary ; Chi-Square Distribution ; Colonic Neoplasms ; surgery ; Colorectal Neoplasms ; surgery ; Colorectal Surgery ; statistics & numerical data ; Disease-Free Survival ; Female ; Humans ; Incidence ; Liver Neoplasms ; secondary ; Logistic Models ; Lung Neoplasms ; secondary ; Lymphatic Metastasis ; physiopathology ; Male ; Middle Aged ; Multivariate Analysis ; Prognosis ; Rectal Neoplasms ; surgery ; Retrospective Studies ; Risk Factors

The function of the spleen in tumor development has been investigated for years. The relationship of the spleen with hepatocellular carcinoma (HCC), a huge health burden worldwide, however, remains unknown. The present study aimed to examine the effect of splenectomy on the development of HCC and the possible mechanism. Mouse hepatic carcinoma lines H22 and Hepa1-6 as well as BALB/c and C57 mice were used to establish orthotopic and metastatic mouse models of liver cancer. Mice were divided into four groups, including control group, splenectomy control group (S group), tumor group (T group) and tumor plus splenectomy group (T+S group). Tumor growth, metastases and overall survival were assessed at determined time points. Meanwhile, myeloid-derived suppressor cells (MDSCs) were isolated from the peripheral blood (PB), the spleen and liver tumors, and then measured by flow cytometery. It was found that liver cancer led to splenomegaly, and increased the percentage of MDSCs in the PB and spleen in the mouse models. Splenectomy inhibited the growth and progression of liver cancer and prolonged the overall survival time of orthotopic and metastatic models, which was accompanied by decreased proportion of MDSCs in the PB and tumors of liver cancer-bearing mouse. It was suggested that splenectomy could be considered an adjuvant therapy to treat liver cancer.
Animals ; Carcinoma, Hepatocellular ; physiopathology ; surgery ; Cell Line, Tumor ; Flow Cytometry ; Humans ; Liver Neoplasms ; physiopathology ; surgery ; Mice ; Myeloid-Derived Suppressor Cells ; pathology ; Neoplasms, Experimental ; physiopathology ; surgery ; Spleen ; physiopathology ; surgery ; Splenectomy ; methods

BACKGROUND/AIMS: Hepatic damage during transarterial chemoembolization (TACE) is a critical complication in patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). Apart from its role in preventing HBV reactivation, there is some evidence for the benefits of preemptive antiviral therapy in TACE. This study evaluated the effect of preemptive antiviral therapy on acute hepatic deterioration following TACE. METHODS: This retrospective observational study included a prospectively collected cohort of 108 patients with HBV-related HCC who underwent TACE between January 2007 and January 2013. Acute hepatic deterioration following TACE was evaluated. Treatment-related hepatic decompensation was defined as newly developed encephalopathy, ascites, variceal bleeding, elevation of the bilirubin level, prolongation of prothrombin time, or elevation of the Child-Pugh score by ≥2 within 2 weeks following TACE. Univariate and multivariate analyses were conducted to identify factors influencing treatment-related decompensation. Preemptive antiviral therapy involves directing prophylaxis only toward high-risk chronic hepatitis B patients in an attempt to prevent the progression of liver disease. We regarded at least 6 months as a significant duration of preemptive antiviral treatment before diagnosis of HCC. RESULTS: Of the 108 patients, 30 (27.8%) patients received preemptive antiviral therapy. Treatment-related decompensation was observed in 25 (23.1%) patients during the follow-up period. Treatment-related decompensation following TACE was observed more frequently in the nonpreemptive group than in the preemptive group (29.5% vs. 6.7%, P=0.008). In the multivariate analysis, higher serum total bilirubin (Hazard ratio [HR] =3.425, P=0.013), hypoalbuminemia (HR=3.990, P=0.015), and absence of antiviral therapy (HR=7.597, P=0.006) were significantly associated with treatment-related hepatic decompensation. CONCLUSIONS: Our findings suggest that preemptive antiviral therapy significantly reduces the risk of acute hepatic deterioration. Preventing hepatic deterioration during TACE by applying such a preemptive approach may facilitate the continuation of anticancer therapy and thus improve long-term outcomes.
Aged ; Antiviral Agents/*therapeutic use ; Bilirubin/blood ; Carcinoma, Hepatocellular/*therapy ; Chemoembolization, Therapeutic/*adverse effects ; Female ; Gastrointestinal Hemorrhage/etiology ; Guanine/*analogs & derivatives/therapeutic use ; Hepatitis B/complications/*drug therapy ; Humans ; Hypoalbuminemia/etiology ; Incidence ; Liver/physiopathology ; Liver Diseases/epidemiology/*etiology ; Liver Neoplasms/*therapy ; Male ; Middle Aged ; Proportional Hazards Models ; Retrospective Studies ; Risk Factors ; Treatment Outcome

OBJECTIVETo investigate the changes in red blood cell count in patients with different liver diseases and the correlation between red blood cell count and degree of liver damage.

METHODSThe clinical data of 1427 patients with primary liver cancer, 172 patients with liver cirrhosis, and 185 patients with hepatitis were collected, and the Child-Pugh class was determined for all patients. The differences in red blood cell count between patients with different liver diseases were retrospectively analyzed, and the correlation between red blood cell count and liver function status was investigated. The Mann-Whitney U test, Kruskal-Wallis H test, rank sum test, Spearman rank sum correlation test, and chi-square test were performed for different types of data.

RESULTSRed blood cell count showed significant differences between patients with chronic hepatitis, liver cancer, and liver cirrhosis and was highest in patients with chronic hepatitis and lowest in patients with liver cirrhosis (P < 0.05). In the patients with liver cirrhosis, red blood cell count tended to decrease in patients with a higher Child-Pugh class (P < 0.05).

CONCLUSIONFor patients with liver cirrhosis, red blood cell count can reflect the degree of liver damage, which may contribute to an improved liver function prediction model for these patients.

Erythrocyte Count ; Hepatitis ; blood ; Humans ; Liver ; physiopathology ; Liver Cirrhosis ; blood ; Liver Neoplasms ; blood ; Retrospective Studies

INTRODUCTIONLarge, recent population-based data for evaluating the predictors of oesophageal variceal bleeding (OVB) among cirrhotic patients is still lacking. This study aimed to determine the cumulative incidence of OVB among cirrhotic patients and identify the predictors of OVB occurrence.

METHODSPatient information on 38,172 cirrhotic patients without a history of OVB, who were discharged between 1 January 2007 and 31 December 2007, was obtained from the Taiwan National Health Insurance Database for this study. All patients were followed up for three years. Death was the competing risk when calculating the cumulative incidences and hazard ratios (HRs) of OVB.

RESULTSOVB was present in 2,609 patients (OVB group) and absent in 35,563 patients (non-OVB group) at hospitalisation. During the three-year follow-up period, the cumulative incidence of OVB was 44.5% and 11.3% in the OVB and non-OVB group, respectively (p < 0.001). Modified Cox regression analysis showed that the HR of OVB history was 4.42 for OVB occurrence (95% confidence interval [CI] 4.13-4.74). Other predictors for OVB occurrence included hepatocellular carcinoma (HR 1.16, 95% CI 1.09-1.24), young age (HR 0.98, 95% CI 0.98-0.98), ascites (HR 1.46, 95% CI 1.37-1.56), alcohol-related disorders (HR 1.20, 95% CI 1.12-1.28), peptic ulcer bleeding (HR 1.26, 95% CI 1.13-1.41) and diabetes mellitus (HR 1.14, 95% CI 1.06-1.23).

CONCLUSIONCirrhotic patients have a fourfold increased risk of future OVB following the first incidence of OVB.

Adult ; Aged ; Alcoholism ; complications ; Ascites ; complications ; Carcinoma, Hepatocellular ; complications ; Databases, Factual ; Diabetes Complications ; Esophageal and Gastric Varices ; epidemiology ; etiology ; Female ; Gastrointestinal Hemorrhage ; epidemiology ; etiology ; Humans ; Incidence ; Liver Cirrhosis ; complications ; physiopathology ; Liver Neoplasms ; complications ; Male ; Middle Aged ; Peptic Ulcer ; complications ; Proportional Hazards Models ; Recurrence ; Retrospective Studies ; Risk ; Taiwan

OBJECTIVE: To investigate the expression of miR-33b in hepatocellular carcinoma (HCC) and to explore regulatory mechanism of miR-33b for cell proliferation of HCC.
 METHODS: HCC tissues and adjacent non-tumor tissues were collected for this study (n=32 for each). Real-time PCR and Western blot were conducted to examine the mRNA and protein expression, respectively. MTT assay was used to detect the cell proliferation. Luciferase reporter gene assay was performed to verify the target relationship between miR-33b and Sal-like 4 (SALL4).
 RESULTS: MiR-33b was significantly downregulated in HCC tissues compared with adjacent non-tumor tissues. Overexpression of miR-33b decreased the proliferation of HCC LH86 cells. SALL4 was identified as a target gene of miR-33b, and its protein expression was negatively regulated by miR-33b. Overexpression of SALL4 reversed the suppressive effect of miR-33b on LH86 cell proliferation. SALL4 was significantly upregulated in HCC tissues compared with adjacent non-tumor tissues.
 CONCLUSION The miR-33b suppresses HCC cell proliferation through down-regulation of SALL4.
Carcinoma, Hepatocellular ; chemistry ; genetics ; physiopathology ; Cell Proliferation ; genetics ; physiology ; Down-Regulation ; Gene Expression Regulation, Neoplastic ; genetics ; physiology ; Humans ; Liver Neoplasms ; MicroRNAs ; analysis ; genetics ; physiology ; RNA, Messenger ; Real-Time Polymerase Chain Reaction ; Transcription Factors ; genetics ; physiology ; Tumor Cells, Cultured ; Up-Regulation

OBJECTIVETo explore the surgical risk, perioperative outcome and the response of patients with hepatocellular carcinoma (HCC) after preoperative transcatheter arterial chemoembolization (TACE).

METHODSA retrospective case-matched study was conducted to compare the characteristics and corresponding measures of patients in the preoperative TACE group and the control group without TACE. A total of 105 patients (82 patients with selective and dynamic region-specific vascular occlusion to perform hepatectomy for patients with complex hepatocellular carcinoma) was included in this study, in which 35 patients underwent TACE therapy, and a 1:2 matched control group of 70 subjects.

RESULTSThe patients of preoperative TACE therapy group had a higher level of γ-glutamyl transpeptidase before operation (119.52±98.83) U/L vs. (67.39±61.25) U/L (P=0.040). The operation time was longer in the TACE group than that in the control group but with a non-significant difference (232.60±95.43) min vs. (218.70±75.13) min (P=0.052). The postoperative recovery of liver function and severe complications in the preoperative TACE group were similar to that in the control group (P>0.05). There were no massive hemorrhage, biliary fistula and 30-d death neither in the treatment group and matched control group.

CONCLUSIONSPreoperative TACE therapy has certain negative effect on liver function. It is preferable to use selective and dynamic region-specific vascular occlusion technique during hepatectomy and combine with reasonable perioperative treatment for this group of patients, that can ensure safety of patients and promote their rapid recovery.

Carcinoma, Hepatocellular ; blood supply ; therapy ; Case-Control Studies ; Chemoembolization, Therapeutic ; adverse effects ; methods ; Hepatectomy ; methods ; Humans ; Liver ; physiopathology ; Liver Neoplasms ; blood supply ; therapy ; Operative Time ; Preoperative Period ; Recovery of Function ; Retrospective Studies ; gamma-Glutamyltransferase ; analysis

OBJECTIVETo detect the expression of interleukin-17A(IL-17A) in hepatocellular carcinoma (HCCs) tissues, and to analyze its relationship with clinicopathological characteristics and epithelial-mesenchymal transition (EMT).

METHODSThe expression of IL-17A, E-cadherin, vimentin proteins and Snail mRNA were detected by immunohistochemistry and in situ hybridization histochemistry in the hepatocellular carcinoma (HCC) tissues of 74 patients.

RESULTSIL-17A staining was detected in 54.1% (40/74) specimens of human HCCs, but only 25.0% (5/20) in corresponding peritumoral tissues (P<0.05). The positive rate of IL-17A expression in HCC patients with grade III+IV and UICC stage III+IV tumors was significantly higher than those with grade I+II and UICC stage I+II tumors. The expression of IL-17A was positively correlated with portal vein tumor thrombus and microvascular invasion (all P<0.05). The 1- and 2-year recurrence-free survival rates were 27.6% and 17.2% in the patients with positive IL-17A expression, but 79.3% and 58.5% in IL-17A-negative HCCs. The 1- and 2-year overall survival rates were 69.0% and 27.8% in the cases with positive IL-17A expression, while 91.3% and 87.0% in IL-17A-negative cases. Patients with IL-17A-positive HCCs showed significantly shorter recurrence-free and overall survival compared with the patients with IL-17A-negative HCCs (P<0.05). Multivariate analysis indicated that IL-17A expression was an independent factor for recurrence-free and overall survival of HCCs. IL-17A-positive HCCs were characterized by increased expression of vimentin (r=0.492, P<0.01) or Snail (r=0.410, P<0.05) and loss of E-cadherin expression (r=-0.404, P<0.05).

CONCLUSIONSOur results suggest that IL-17A is closely related to epithelial-mesenchymal transition in hepatocellular carcinoma. IL-17A-positive hepatocellular carcinoma demonstrates more aggressive biological behavior, and IL-17A may serve as a potential prognostic marker for this cancer.

Cadherins ; genetics ; metabolism ; Carcinoma, Hepatocellular ; metabolism ; mortality ; pathology ; physiopathology ; Disease-Free Survival ; Epithelial-Mesenchymal Transition ; Humans ; Immunohistochemistry ; Interleukin-17 ; metabolism ; Liver Neoplasms ; metabolism ; mortality ; pathology ; physiopathology ; Neoplasm Invasiveness ; Neoplasm Proteins ; genetics ; metabolism ; Neoplasm Recurrence, Local ; Prognosis ; RNA, Messenger ; metabolism ; Snail Family Transcription Factors ; Survival Rate ; Transcription Factors ; genetics ; metabolism ; Vimentin ; genetics ; metabolism

Surgical resection is the best treatment for hepatocarcinoma. With the rapid development and cooperation of multi-disciplines, the liver surgery gradually towards a precise stage, and accurate evaluation of regional liver function preoperatively is demand for the development of precise liver surgery. Methods to assess function of liver at present include serological liver function and biochemical examination, clinical liver function scoring system, quantitative liver function test and imaging examination. Nuclide imaging technology and liver specificity enhanced MRI contrast agent are expected to achieve to evaluate regional liver function.
Carcinoma, Hepatocellular ; physiopathology ; Contrast Media ; Liver Function Tests ; Liver Neoplasms ; physiopathology ; Magnetic Resonance Imaging ; Sensitivity and Specificity