Identification of novel hub genes associated with gastric cancer using integrated bioinformatics analysis.

BACKGROUND: Gastric cancer (GC) is one of the most common solid malignant tumors worldwide with a high-recurrence-rate. Identifying the molecular signatures and specific biomarkers of GC might provide novel clues for GC prognosis and targeted therapy. METHODS: Gene expression profiles were obtained from the ArrayExpress and Gene Expression Omnibus database. Differentially expressed genes (DEGs) were picked out by R software. The hub genes were screened by cytohubba plugin. Their prognostic values were assessed by Kaplan-Meier survival analyses and the gene expression profiling interactive analysis (GEPIA). Finally, qRT-PCR in GC tissue samples was established to validate these DEGs. RESULTS: Total of 295 DEGs were identified between GC and their corresponding normal adjacent tissue samples in E-MTAB-1440, GSE79973, GSE19826, GSE13911, GSE27342, GSE33335 and GSE56807 datasets, including 117 up-regulated and 178 down-regulated genes. Among them, 7 vital upregulated genes (HMMR, SPP1, FN1, CCNB1, CXCL8, MAD2L1 and CCNA2) were selected. Most of them had a significantly worse prognosis except SPP1. Using qRT-PCR, we validated that their transcriptions in our GC tumor tissue were upregulated except SPP1 and FN1, which correlated with tumor relapse and predicts poorer prognosis in GC patients. CONCLUSIONS: We have identified 5 upregulated DEGs (HMMR, CCNB1, CXCL8, MAD2L1, and CCNA2) in GC patients with poor prognosis using integrated bioinformatical methods, which could be potential biomarkers and therapeutic targets for GC treatment.

Effect of Inflammation on Fibrosis Staging Measured by Quantitative Elasticity Parameters in Rats With Immune Hepatitis.

OBJECTIVES: To investigate the effect of inflammation on fibrosis staging measured by quantitative elasticity parameters in rats with immune hepatitis. METHODS: Fifty-two rats were injected with swine serum as a model group, whereas 8 rats were injected with saline as a control group. Rats were randomly subjected to real-time tissue elastography biweekly. Tissue dispersion quantitative analysis was performed to obtain 12 quantitative elasticity parameters: relative mean value, standard deviation, blue area percentage, complexity, kurtosis, skewness, contrast, entropy, inverse difference moment, angular second moment, correlation, and liver fibrosis index. Subsequently, rats were euthanized, and liver specimens were taken for pathologic examination. The Kruskal-Wallis test was used for comparisons among groups. Spearman rank correlation analysis was used for correlation analysis. Receiver operating characteristic curves were used to optimize cutoff values and evaluate the diagnostic performance of the liver fibrosis index. RESULTS: Except for complexity, kurtosis, and correlation, the other 9 parameters had statistical differences (P < .05), and among these 9 parameters, the liver fibrosis index had the strongest correlation with fibrosis staging (r = 0.809; P < .05). Except for kurtosis and correlation, the other 10 parameters had statistical differences (P < .05), and among these 10 parameters, the liver fibrosis index had the highest correlation with inflammation grading (r= 0.766; P< .05). The fibrosis index cutoff values were 2.35 for stage S1 or higher (area under the curve [AUC], 0.940; sensitivity, 97.1%; specificity, 73.3%), 2.99 for stage S2 or higher (AUC, 0.865; sensitivity, 78.6%; specificity, 81.0%), 3.48 for stage S3 or higher (AUC, 0.924; sensitivity, 94.4%; specificity, 87.1%), and 4.05 for stage S4 (AUC, 0.933; sensitivity, 87.5%; specificity, 95.1%). CONCLUSIONS: Real-time elastography could be used to noninvasively evaluate fibrosis staging in rats with immune hepatitis. However, inflammation had an effect on the accuracy of this technique.

[Identification of genes regulated by HBV preS1-transactivated protein 2 binding protein 1].

OBJECTIVE: To identify genes regulated by HBV preS1-transactivated protein 2 binding protein 1 (PS1TP2BP1). METHODS: PS1TP2BP1 gene was amplified by polymerase chain reaction (PCR) technique and cloned into the eukaryotic expression vector pcDNA 3.1/my-c-His A. The mRNAs isolated from HepG2 cells transfected recombinant eukaryotic expression vector pcDNA 3.1/myc-HisA-PS1TP2BP1 and pcDNA 3.1/myc-HisA empty vector were used to construct subtractive library. The differentially expressed genes were identified and analyzed. RESULTS: 35 differentially expressed clones were obtained. Colony PCR identified 15 clones with 200-1000 bp inserts. Sequence analysis identified 15 differentially expressed genes. CONCLUSION: This study provides data for further characterize the function of PS1TP2BP1.

Mismatch repair-deficient status associates with favorable prognosis of Eastern Chinese population with sporadic colorectal cancer.

The present study aimed to investigate the expression level of DNA mismatch repair gene (MMR) in in sporadic colorectal cancer (SCRC) in eastern China, and to investigate the association between MMR status and prognosis of patients with SCRC. Patient archives from the Department of Gastrointestinal Surgery of Weihai Municipal Hospital (Weihai, China) were retrospectively collected between January 2011 and January 2012. Of the 221 consecutive patients identified, 192 patients who met the criterion were deemed eligible for inclusion. Immunohistochemistry (IHC) was conducted to detect the expression of MMR proteins MutL homolog 1 (MLH1), MutS homolog 2 (MSH2), MSH6 and PMS1 homolog 2, mismatch repair system component (PMS2) expression and mutation in sporadic colorectal cancer (SCRC). Kaplan-Meier plots and log-rank tests were performed to conduct survival analysis and Cox proportional hazard regression models were conducted to determine independent prognostic factors. The total rate of deficient MMR (dMMR) was 14.58% (28/192): MSH6, 0.52% (1/192); PMS2, 4.17% (8/192); MSH2/MSH6, 3.65% (7/192); and MLH1/PMS2, 6.25% (12/192). The dMMR group had a significantly longer overall survival time compared with proficient MMR (pMMR) group (P=0.017). Disease-free survival time of dMMR group was also longer than pMMR group (P=0.027). Multivariate analysis using the Cox regression model confirmed that MMR status was an independent prognostic factor for SCRC. Loss of MMR expression was indicative of a favorable outcome for patients with SCRC, and MMR status could be viewed as an independent prognostic factor.

Characteristics of focal liver lesions in arterial phase on contrast-enhanced ultrasound and contrast--enhanced computed tomography - comparative study.

BACKGROUND: To compare the features of focal liver lesions in the arterial phase on contrast-enhanced ultrasonography (CEUS) and contrast-enhanced computed tomography (CECT). MATERIAL AND METHODS: A total of 38 lesions in 29 patients with focal liver lesions (FLL) were examined with CEUS and CECT. The characteristics of the enhancement were determined, especially in the early arterial phase (0~25 s). The enhancement of FLL in CEUS and CECT graded as follows: grade 0 - no enhancement; grade I - peripheral enhancement or spotty enhancement at the center; grade II - spoke-like, honeycomb-like or heterogeneous enhancement; grade II - entire enhancement. RESULTS: On CEUS, the arriving time within 25 s was found in 36 out of 38 lesions (94.73%) and the peak time within 25 s in 29 lesions (76.32%). The number of grade II-III FLL was 25 (65.79%) on CEUS, and 13 (34.21%) on CECT showing a significant difference (p < 0.05). CONCLUSIONS: Compared with CECT, CEUS plays an important role in the diagnosis of FLL with enhancement in the early arterial phase (< 25 s).

Quantitative analysis of real-time tissue elastography for evaluation of liver fibrosis.

UNLABELLED: The present study aimed to investigate the feasibility of quantitative analysis of liver fibrosis using real-time tissue elastography (RTE) and its pathological and molecule biological basis. METHODS: Fifty-four New Zealand rabbits were subcutaneously injected with thioacetamide (TAA) to induce liver fibrosis as the model group, and another eight New Zealand rabbits served as the normal control group. Four rabbits were randomly taken every two weeks for real-time tissue elastography (RTE) and quantitative analysis of tissue diffusion. The obtained twelve characteristic quantities included relative mean value (MEAN), standard deviation (SD), blue area % (% AREA), complexity (COMP), kurtosis (KURT), skewness (SKEW), contrast (CONT), entropy (ENT), inverse different moment (IDM), angular secon moment (ASM), correlation (CORR) and liver fibrosis index (LF Index). Rabbits were executed and liver tissues were taken for pathological staging of liver fibrosis (grouped by pathological stage into S0 group, S1 group, S2 group, S3 group and S4 group). In addition, the collagen I (Col I) and collagen III (Col III) expression levels in liver tissue were detected by Western blot. RESULTS: Except for KURT, there were significant differences among the other eleven characteristic quantities (P < 0.05). LF Index, Col I and Col III expression levels showed a rising trend with increased pathological staging of liver fibrosis, presenting a positive correlation with the pathological staging of liver fibrosis (r = 0.718, r = 0.693, r = 0.611, P < 0.05). CONCLUSION: RTE quantitative analysis is expected for noninvasive evaluation of the pathological staging of liver fibrosis.

[A 3-year-follow-up study on the prognosis of 'two-route chemotherapy' on liver cancer patients with portal vein tumor thrombus].

OBJECTIVE: To study the achievements and safety of Transcatheter arterial chemoembolization (TACE) associated Portal Vein Chemo-therapy (PVC) per-drug delivery system (DDS) program in preventing the recurrence of hepatic cell cancer (HCC) and Portal Vein Tumor Thrombus (PVTT). METHODS: 97 cases with HCC and PVTT were treated from January 2009 to January 2011. Patients with tumor or tumor thrombus were resected on all the cases and randomly divided into 3 groups. TACE, PVC per-DDS TACE and PVC per-DDS were given to group A, group B, and group C, respectively. Patients in the 3 groups were followed and compared on the Disease Free Survivals (DFS) and the accumulative survival rates, at 6 months, 1 year and 2 years after the operation. RESULTS: After the surgery was completed in June, the 1-year, 2-year, 3-year survival rates and cumulative survival rate in group C was higher than in group A or group. Significant differences did not appear in June but did show in 1 year after the surgery (P > 0.05) as well as in both 2 and 3 years, after the surgery (P < 0.01). CONCLUSION: Patients with HCC and PVTT, the TACE chemotherapy in association with PVC per-DDS could increase both the DFSs and accumulative survival rates, when compared to the either single TACE or PVC per-DDS, after the tumor or tumor thrombus were resected.