Systemic transcriptome analysis of hepatocellular carcinoma.

Liver cancer is one of the most common malignant tumors, and most of which is hepatocellular carcinoma (HCC). We aim to study the characteristic changes of numerous genes and their roles in HCC through systematical analysis of the characteristics of expression spectrum of HCC. Firstly, we made systematic clustering of the HCC samples according to the RNAseq data from TCGA (The Cancer Genome Atlas) and newly classified HCC. Then the characteristic genes in different molecular subtypes were found out and further analyzed combing with methylation and SNP 6.0 chip. Finally, these genes were subjected to do functional annotation and abnormal signaling pathways of HCC in various molecular subtypes and were screened out. There were 3843 differential genes screened; among which, 689 genes were enriched into 13 KEGG-related pathways, and the expression of 27 and 924 genes showed positive and negative correlation to methylation level, respectively, while the expression of 43 genes showed positive correlation to variation level of copy number. The methylation degree of ZSCAN18 may be considered as a marker for prognosis evaluation, and ABHD6 could be a potential anti-oncogene.

Comprehensive Analysis of the Expression of TGF-ß Signaling Regulators and Prognosis in Human Esophageal Cancer.

More and more evidences show that TGF-ß has a crucial role in tumor initiation and development. However, the mechanism of the TGF-ß signal regulator in esophageal cancer (EC) is still unclear. Here, we use a variety of bioinformatics methods to analyze the expression and survival data of TGF-ß signal regulators in patients with EC. We extracted the expression of the S-TGF-ß signal regulator from The Cancer Genome Atlas (TCGA). The cBioPortal database was used to assess the frequency of genetic variation. The TGF-ß signal regulator is expressed in EC and normal tissues. The objective is to use the Kaplan-Meier plotter database to investigate the prognostic value of TGF-ß signal regulators in cancer patients. The DAVID and clusterProfiler software package were used for functional enrichment analysis. We found that patients with TGF-ß signaling mutations have shorter overall survival, disease-free survival, disease-specific survival, platinum overall survival, and platinum-free progression survival. We found that compared with the noncancerous tissues of patients with EC, ZFYVE9, BMPR1B, TGFB3, TGFBRAP1, ACVRL1, TGFBR2, SMAD4, SMAD7, ACVR2A, BMPR1, and SMAD9 were significantly downregulated in tumor tissues, while ACVR1 and Smad1 were significantly upregulated in tumor samples. Univariate survival analysis showed that ACVR1, TGFBR3, TGFBRAP1, BMPR1A, SMAD4, and TGFBR2 were positively correlated with overall survival (OS) prolongation. In addition, TGF-ß signal transduction regulators could be divided into two classes. Subclass 1 was involved in regulating cell adhesion, PI3K-Akt signaling, and Rap1 signaling. Subclass 2 was related to regulating angiogenesis and PI3K signaling. In short, all members of TGF-ß signal regulators can be used as biomarkers to predict the prognosis of patients with EC.

[Improved Regression Kriging Prediction of the Spatial Distribution of the Soil Cadmium by Integrating Natural and Human Factors].

Mastering the spatial distribution of heavy metals in the soil plays an important supporting role in the scientific formulation of soil pollution risk management and control strategies. Few factors were considered and multiple collinearity between parallel variables existed,resulting in low prediction accuracy. OK (common Kriging method), NRK (regressive Kriging method based on natural factors only), and NARK (regressive Kriging based on natural-human factors)were used to simulate the spatial distribution of soil Cd by selecting 23 natural-artificial influencing factors. The prediction accuracy was evaluated based on an empirical study of the area around Shaoguan Qujiang smelter. The results showed that the above-standard rate of soil cadmium in this area reached 85.93%, and the effect on the spatial heterogeneity of soil cadmium was shown as air emissions from smelters > air emissions from steel plants > pH > organic matter > Euclidean distance to road > Euclidean distance to river. The root-mean-square error and average absolute error of NARK's prediction results for soil cadmium were 26.86% and 30.56% lower than that of the OK method, respectively. The model determination coefficient R2 increased from 0.78 to 0.88. Compared with that of NRK, it was reduced by 24.15% and 24.23% and R2 increased from 0.81 to 0.88. The NRK combining natural and human factors significantly improved the simulation accuracy of the spatial distribution of soil cadmium, and the addition of human factors as auxiliary variables, especially atmospheric point source pollution emissions, greatly contributed to the improvement of the model accuracy.

FOXR2 Promotes the Proliferation, Invasion, and Epithelial-Mesenchymal Transition in Human Colorectal Cancer Cells.

Forkhead box R2 (FOXR2), a member of the FOX gene family, has not been very well investigated for its role in cancer. A recent study has shown that FOXR2 is highly expressed in breast cancer samples and is associated with poor prognosis. In addition, FOXR2 was identified as an oncogene in medulloblastoma. Nevertheless, whether FOXR2 plays a role in colorectal cancer (CRC) remains unclear. In the present study, we conducted several in vitro and in vivo studies to investigate the expression and effect of FOXR2 in CRC. The study results demonstrated that FOXR2 was upregulated in CRC tissues and cells. Downregulation of FOXR2 inhibited CRC cell proliferation, invasion, and the epithelial-mesenchymal transition (EMT) phenotype in vitro and also suppressed CRC cell growth and metastasis in vivo. Furthermore, downregulation of FOXR2 remarkably reduced the protein expression of Shh, Gli1, and Ptch1 in SW480 cells. Taken together, our data suggested that FOXR2 significantly promoted proliferation, invasion, and EMT of CRC cells. All these findings provided evidence for the role of FOXR2 as an oncogene in CRC development.

Endoscopic versus laparoscopic resection of gastric gastrointestinal stromal tumors: a multicenter study.

Despite endoscopic resection has been performed to treat gastric gastrointestinal stromal tumor (GISTs). However, the safety and long-term outcomes remains controversial. This study aims to compare the safety and surgical outcomes of endoscopic versus laparoscopic resection of gastric GISTs. A total of 335 patients that were pathologically confirmed with gastric GISTs (tumor size ≤ 3.5 cm) were surgically treated with endoscopic resection (endoscopic group) or laparoscopic resection (laparoscopic group) in three institutions from March 1, 2011 to October 1 2014. These demographics, tumor characteristics, and outcomes were retrospectively analyzed for identification of outcomes and feasibility of endoscopic or laparoscopic resection. Of 335 patients, 262 and 73 patients underwent endoscopic and laparoscopic resection, respectively. The average tumor size was 1.33±0.78 cm in the endoscopic group and 1.97±0.93 cm in the laparoscopic group. The average operating time was 62.40±36.94 min in the endoscopic group and 112.81±55.69 cm in the laparoscopic group. Days of realimentation was 2.76±1.67 in the endoscopic group and 4.89±2.03 in the laparoscopic group. The average cost was $ 3246.01±1017.61 in the endoscopic group and $ 4884.81±1339.51 in the laparoscopic group. There was no postoperative mortality. Endoscopic resection for gastric GISTs is safe and feasible in tumors ≤ 3.5 cm. Because endoscopic resection showed good results with lower operating time, realimentation days, length of hospital stay and mean total cost, it is a minimally invasive and safe alternative approach which can achieve fast recovery and satisfactory outcomes for appropriately selected patients with gastric GISTs.

The effects of the insulin resistance index on the virologic response to entecavir in patients with HBeAg-positive chronic hepatitis B and nonalcoholic fatty liver disease.

PURPOSE: To further observe and verify the effect of nonalcoholic fatty liver disease (NAFLD) on the response to antiviral therapy in patients with chronic hepatitis B (CHB) and investigate the relationship between the virologic response and insulin resistance. PATIENTS AND METHODS: A retrospective study was adopted and 61 NAFLD patients with HBeAg-positive CHB were included as the observation group (group A), and 64 patients with simple CHB were included as the control group (group B). RESULTS: After 12 weeks of treatment with entecavir, the total virologic response rate in group A was statistically significantly lower than that in group B (P<0.05). During weeks 24-96, the difference was not statistically significant (P>0.05). In weeks 48 and 96, there was no significant difference in the HBeAg seroconversion rates between the two groups (P>0.05). In weeks 12 and 24, there was also no significant difference in the alanine transaminase (ALT) normalization rate between the two groups (P>0.05). Then, in weeks 48 and 96, the ALT normalization rate of group A was obviously lower than that of group B (P<0.05). Group A patients were divided into group A1 (≤M) and group A2 (>M) according to the median value (M=2.79) of the baseline homeostatic model assessment method insulin resistance levels. In weeks 48 and 96, the ALT normalization rate of group A1 was significantly higher than that of group A2 (P<0.05). The correlation coefficient (r) of the baseline homeostatic model assessment method insulin resistance level and the severity of fatty liver in group A was 0.426 (P=0.001). CONCLUSION: NAFLD cannot affect the long-term total virologic response rate and HBeAg seroconversion rate in CHB patients treated with entecavir but can reduce the long-term biochemical response rate, which has a positive correlation with the severity of fatty liver and the insulin resistance index.

Effects of CDC42 on the proliferation and invasion of gastric cancer cells.

Cell division cycle 42 (CDC42), which is a member of the Rho GTPase family, has been reported to regulate the metastasis of various human cancer cells; however, the role of CDC42 in gastric cancer (GC) remains unclear. The present study aimed to investigate the effects of CDC42 on the proliferation, migration and invasion of GC. Furthermore, the molecular mechanisms underlying the effects of CDC42 on GC were explored. The expression levels of CDC42 in the AGS and SGC7901 human GC cell lines were reduced by RNA interference. Knockdown of CDC42 significantly inhibited the proliferation of AGS and SGC7901 cells, and it was suggested that this inhibitory process may be due to cell cycle arrest at G1/S phase and downregulation of cyclin A, cyclin D1, cyclin E and proliferating cell nuclear antigen. Furthermore, knockdown of CDC42 markedly inhibited the migration and invasion of GC cells, and suppressed the expression of matrix metalloproteinase 9. These results indicated that CDC42 is a key regulator involved in regulating the proliferation, migration and invasion of GC, and it may be considered a potential therapeutic target in GC.

Methylation status of TRAF2 is associated with the diagnosis and prognosis of gastric cancer.

The purpose was to investigate whether the expression level of TRAF2 gene was regulated by DNA methylation and explore the role of TRAF2 methylation in the diagnosis and prognosis of gastric cancer (GC). Firstly, we detected the expression of TRAF2 both at mRNA level and protein level. And the up-regulated of TRAF2 expression at two different levels were both found (P<0.001). Then we measured the methylated status of TRAF2 by MSP and got a result of that TRAF2 was hypomethylated in GC patients compared with healthy controls (P<0.001). Meanwhile, the relationship between TRAF2 methylation and clinicopathologic characteristics was estimated through chi-square. The outcome proved that TRAF2 methylation was impacted by age (P=0.024), lymph node metastasis (P=0.046), TNM stage (P=0.021), distant metastasis (P=0.002) and depth of invasion (P=0.002). The AUC of 0.795 accompanying a sensitivity of 66.7% and a specificity of 94.7% were obtained from Receiver Operating Characteristic (ROC) curve which indicated the diagnostic value of TRAF2 methylation was high. At last, we researched the prognostic value of TRAF2 methylation. Kaplan-Meier showed that patients with TRAF2 hypomethylation had lived much shorter than those with TRAF2 hypermethylation (log rank test, P<0.001). Cox regression analysis revealed TRAF2 hypomethylation (HR=18.827, 95% CI=3.103-114.222, P=0.001), lymph node metastasis (HR=0.154, 95% CI=0.047-0.512, P=0.002), distant metastasis (HR=3.032, 95% CI=1.116-8.237, P=0.030), as well as differentiation (HR=0.287, 95% CI=0.113-0.731, P=0.009) were all vital prognostic factors in GC. Taken together, TRAF2 expression was increased in GC patients by DNA hypomethylation and this methylation could be an independent diagnostic and prognostic indicator in GC.

CDH1 promoter polymorphism (-347G-->GA) is a possible prognostic factor in sporadic colorectal cancer.

AIM: To investigate the role of the -347G-->GA polymorphism in the progression of colorectal cancer (CRC). METHODS: We designed a case-control study based on a population of CRC patients in China and normal healthy controls with no history of tumors or inherited diseases. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analyses were used to genotype the variants, and immunohistochemical staining was performed to measure the expression of E-cadherin in different allele cases among the CRC patients and normal controls. RESULTS: The GA-allele (G/GA heterozygous and GA/GA homozygous) did not increase the risk of CRC compared with the G-allele (OR=1.232, 95% CI=0.898-1.691). However, the frequencies of the GA-allele were higher in poorly differentiated (P=0.002) and proximal (P=0.019) CRC patients than in normal controls. We also observed that E-cadherin expression was lower in poorly differentiated CRC patients than in well differentiated CRC patients (P=0.001). Furthermore, E-cadherin expression was lower for the GA-allele than for the G-allele (G/G heterozygous) in CRC patients (P=0.018). In contrast, there was no significant difference in E-cadherin expression for the G-allele and GA-allele in normal controls (P=0.292). CONCLUSION: The -347G-->GA promoter polymorphism in E-cadherin gene is associated with specific CRC features, and may be a prognostic factor rather than a susceptibility factor during the progression of CRC.