GNG4 Promotes Tumor Progression in Colorectal Cancer.

Colorectal cancer is a common digestive system tumor, which lacks effective therapeutic targets and biomarkers to accurately determine the prognosis. Sequencing data, immunohistochemistry, and Kaplan-Meier analysis were used to explore GNG4 clinical significance in colorectal cancer. And, through in vitro experiments, the effects of GNG4 on cell behaviors were investigated. The results showed that the mRNA and protein expression levels of GNG4 in patients with colorectal cancer were significantly higher than in normal people. The patients with high GNG4 expression had a worse prognosis than patients with low GNG4 expression. The in vitro experiments presented that after downregulating the expression of GNG4, proliferation, migration, and invasion of SW-620 colon cancer cells were all significantly reduced, apoptosis was significantly increased, and the cell cycle was blocked in the S phase. In summary, GNG4 may be of importance in the therapy of the colorectal cancer; therefore, targeting GNG4 may have certain clinical value in the treatment of colorectal cancer.

Diagnostic significance and potential function of miR-338-5p in hepatocellular carcinoma: A bioinformatics study with microarray and RNA sequencing data.

MicroRNA (miR)-338-5p has been studied in hepatocellular carcinoma (HCC); however, the diagnostic value and molecular mechanism underlying its actions remains to be elucidated. The present study aimed to validate the diagnostic ability of miR­338­5p and further explore the underlying molecular mechanism. Data from eligible studies, Gene Expression Omnibus (GEO) chips and The Cancer Genome Atlas (TCGA) datasets were gathered in the data mining and the integrated meta­analysis, to evaluate the significance of miR­338­5p in diagnosing HCC comprehensively. The potential target genes of miR­338­5p were achieved from the intersection of the deregulated targets of miR­338­5p from GEO and TCGA in addition to the predicted target genes from 12 online software. A protein­protein­interaction (PPI) network was drawn to illustrate the interaction between target genes and to define the hub genes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to investigate the function of the target genes. From the results, miR­338­5p exhibited favorable value in diagnosing HCC. Types of sample and experiment were defined as the possible sources of heterogeneity in meta­analysis. A total of 423 genes were selected as the potential target genes of miR­338­5p, and five genes were defined as the hub genes from the PPI network. The GO and KEGG analyses indicated that the target genes were significantly assembled in the pathways of metabolic process and cell cycle. miR­338­5p may function as a novel diagnostic target for HCC through regulating certain target genes and signaling pathways.

Prognostic microRNAs and their potential molecular mechanism in pancreatic cancer: A study based on The Cancer Genome Atlas and bioinformatics investigation.

Although certain biomarkers that are directly associated with the overall survival (OS) of patients with pancreatic adenocarcinoma (PAAD) have been identified, the efficacy of a single factor is limited to predicting the prognosis. The aim of the present study was to identify a combination micro (mi)RNA signature that enhanced the prognostic prediction for PAAD. Following analysis of the data available from The Cancer Genome Atlas (TCGA), 175 PAAD samples were selected for the present study, and the associations between 494 miRNAs and OS were investigated. The prognostic value of all miRNAs was analyzed by multivariate Cox regression, and the miRNAs were ranked according to the hazard ratio (HR) and P­values. The top 5 miRNAs (miR­1301, miR­125a, miR­376c, miR­328 and miR­376b) were significantly associated with OS (HR=0.139; 95% confidence interval, 0.043­0.443; P<0.001), thus demonstrating that this panel was able to serve as an independent prognostic factor for PAAD. In addition, the present study also predicted the target genes of the top 10 miRNAs with the highest prognostic values using 12 different prediction software, and enrichment signaling pathway analyses elucidated that several pathways may be markedly associated with these miRNAs, including 'Pathways in cancer', 'Chronic myeloid leukemia', 'Glioma' and 'MicroRNAs in cancer'. Lastly, ubiquitin C, epidermal growth factor receptor, estrogen receptor 1, mitogen­activated protein kinase 1, mothers against decapentaplegic homolog 4 and androgen receptor may be the hub genes revealed by STRING analysis. The present study identified several miRNAs, particularly a five­miRNA­pool, that may be reliable, independent factors for predicting survival in patients with PAAD. However, the underlying molecular mechanisms require further investigation in the future.

The protective value of miR-204-5p for prognosis and its potential gene network in various malignancies: a comprehensive exploration based on RNA-seq high-throughput data and bioinformatics.

PURPOSE: The prognostic role of miR-204-5p (previous ID: miR-204) is varied and inconclusive in diverse types of malignant neoplasm. Therefore, the purposes of the study comprehensively explore the overall prognostic role of miR-204-5p based on high-throughput microRNA sequencing data, and to investigate the potential role of miR-204-5p via bioinformatics approaches. MATERIALS AND METHODS: The data of microRNA sequencing and survival were downloaded from The Cancer Genome Atlas (TCGA), and the prognostic value of miR-204-5p was analyzed by using Kaplan-Meier and univariate cox regressions. Then a meta-analysis was conducted with all TCGA data and relevant studies collected from literature. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated. The prospective molecular mechanism of miR-204-5p was also assessed at a functional level with Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and protein-to-protein interactions (PPI) network. RESULTS: From TCGA data, the prognostic value of miR-204-5p obviously varied among 20 types of cancers. The pooled HR was 0.928 (95% CI: 0.774-1.113, P = 0.386, 6203 cases of malignancies). For the meta-analysis based on 15 studies from literature, the pooled HR was 0.420 (95% CI: 0.306-0.576, P < 0.001, 1783 cases of malignancies) for overall survival (OS). Furthermore, the combined HR from both TCGA and literature was 0.708 (95% CI: 0.600-0.834, P < 0.001, 7986 cases of malignancies). Subgroup analyses revealed that miR-204-5p could act as a prognostic marker in cancers of respiratory system and digestive system. Functional analysis was conducted on genes predicted as targets (n = 2057) after the overlay genes from six out of twelve software were extracted. Two significant KEGG pathways were enriched (hsa04360: Axon guidance and hsa04722: Neurotrophin signaling pathway). PPI network revealed some hub genes/proteins (CDC42, SOS1, PIK3R1, MAPK1, PLCG1, ESR1, MAPK11, and AR). CONCLUSIONS: The current study demonstrates that over-expression of miR-204-5p could be a protective factor for a certain group of cancers. Clinically, the low miR-204-5p level could gain a predictive value for a poor survival in cancers of respiratory system and digestive system. The detailed molecular mechanisms of miR-204-5p remain to be verified.

RNA-sequencing investigation identifies an effective risk score generated by three novel lncRNAs for the survival of papillary thyroid cancer patients.

Scholars are striving to apply molecular biology involving long non-coding RNA (lncRNA) in the prognostication of papillary thyroid cancer (PTC). However, the clinical role of lncRNAs in the prognostic setting of PTC is still unclear. Herein, a comprehensive inquiry was performed to screen lncRNA expression profiling with 507 PTC patients from The Cancer Genome Atlas RNA-sequencing datasets. A total of 734 lncRNAs were detected to be aberrantly expressed, among which three novel lncRNAs including AC079630.2, CRNDE and CTD-2171N6.1 were markedly related to the progression and survival of PTC. Furthermore, the aberrant expression of these lncRNAs could be verified by other cohorts from gene expression omnibus (GEO) as detected by microarrays. Next, we established a three-lncRNA signature and divided the PTC patients into two subgroups of high- and low-risk. Interestingly, patients with high-risk tended to gain obviously poorer outcome. Most importantly, this three-lncRNA signature was an independent biomarker to predict the patient survival of PTC. The accurate molecular roles of these three lncRNAs remains unclarified and warrants further characterization, but our current data propose that they might play pivotal roles in PTC tumorigenesis and more importantly, these novel lncRNAs are closely related to patients' survival. These discoveries will have far-reaching consequences with respect to molecular prediction of PTC.

Down-regulation of miR-26a-5p in hepatocellular carcinoma: A qRT-PCR and bioinformatics study.

BACKGROUND: To practically verify the clinical value of miR-26a-5p and thoroughly explore its target genes as well as its potential functions in hepatocellular carcinoma (HCC). METHODS: HCC and adjacent non-cancerous hepatic tissues of 95 HCC patients were collected for analysis using reverse transcription quantitative real-time PCR (qRT-PCR). For the bioinformatics analysis, we identified potential target genes for miR-26a-5p from differentially expressed genes (DEGs) in Gene Expression Omnibus (GEO) data sets and miRWalk predicted database. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and protein-protein interaction (PPI) analyses were applied to analyze the prospective mechanisms of the predicted target genes. RESULTS: MiR-26a-5p showed a significantly lower expression level in HCC tissues (1.56±1.07) than adjacent benign liver tissues (2.28±1.06, P<0.001). The area under the curve (AUC) of the receiver operating characteristic (ROC) was 0.665 (95% CI: 0.588-0.743, P<0.001). Significant correlations between miR-26a-5p expression and clinicopathological features such as gender (r=0.275, P<0.01), clinical TNM stage (r=-0.306, P<0.01), and metastasis (r=-0.321, P<0.01) were observed. To examine potential target genes, we obtained 175 genes for further function analysis, by attaining the intersection of 2062 up-regulated DEGs and 1390 online-predicted target genes. The GO and KEGG pathway annotation indicated focal adhesion, regulation of actin cytoskeleton and the PI3K-Akt signaling pathway as significant prospective mechanisms. The PPI network indicated that NRAS was the most essential hub gene in the whole network. CONCLUSION: Down-regulated miR-26a-5p was closely correlated with the status of metastasis and the progression of HCC. MiR-26a-5p might play protective roles by targeting diverse genes and pathways.

Downregulation of miR­136­5p in hepatocellular carcinoma and its clinicopathological significance.

The clinical significance of microRNA (miR)­136­5p in hepatocellular carcinoma (HCC) has not been verified. Therefore, in the current study, the authors aimed to explore miR­136­5p expression and its clinical significance in HCC, as well as to investigate its potential target genes function. The authors detected the levels of miR­136­5p in 101 pairs of HCC and para­cancer tissues via reverse transcription­quantitative polymerase chain reaction. Gene Expression Omnibus database and the Cancer Genome Atlas (TCGA) database were used to further verify the clinical significance of miR­136­5p expression in HCC. The target genes prediction analysis of miR­136­5p, natural language processing (NLP) analysis of HCC in PubMed and gene functional enrichment analysis were conducted. The miR­136­5p level was markedly downregulated in HCC tissue, compared to para­non­tumor tissue. MiR­136­5p expression decreased in HCC patients with metastasis (P=0.004), advance TNM stage (P<0.001), portal vein tumor embolus (P=0.007) and vaso­invasion (P=0.003), compared with those HCC patients with non­metastasis, early TNM stage, non­portal vein tumor embolus and non­vaso­invasion, respectively. In the TCGA database, downregulated miR­136­5p was also observed in HCC tissue compared to normal liver tissue (P<0.001). There were 178 genes obtained from the overlap between predicted targets and NLP analysis. GO and KEGG pathway analyses revealed some significant pathways related to cancers. Downregulation of miR­136­5p may be responsible for the carcinogenesis and aggressiveness of HCC. miR­136­5p may act as an anti­carcinoma miRNA, which is essential for HCC progression through the regulation of various signaling pathways. Thus, miR­136­5p interaction may provide a novel strategy for HCC treatment.

From big data to diagnosis and prognosis: gene expression signatures in liver hepatocellular carcinoma.

BACKGROUND: Liver hepatocellular carcinoma accounts for the overwhelming majority of primary liver cancers and its belated diagnosis and poor prognosis call for novel biomarkers to be discovered, which, in the era of big data, innovative bioinformatics and computational techniques can prove to be highly helpful in. METHODS: Big data aggregated from The Cancer Genome Atlas and Natural Language Processing were integrated to generate differentially expressed genes. Relevant signaling pathways of differentially expressed genes went through Gene Ontology enrichment analysis, Kyoto Encyclopedia of Genes and Genomes and Panther pathway enrichment analysis and protein-protein interaction network. The pathway ranked high in the enrichment analysis was further investigated, and selected genes with top priority were evaluated and assessed in terms of their diagnostic and prognostic values. RESULTS: A list of 389 genes was generated by overlapping genes from The Cancer Genome Atlas and Natural Language Processing. Three pathways demonstrated top priorities, and the one with specific associations with cancers, 'pathways in cancer,' was analyzed with its four highlighted genes, namely, BIRC5, E2F1, CCNE1, and CDKN2A, which were validated using Oncomine. The detection pool composed of the four genes presented satisfactory diagnostic power with an outstanding integrated AUC of 0.990 (95% CI [0.982-0.998], P < 0.001, sensitivity: 96.0%, specificity: 96.5%). BIRC5 (P = 0.021) and CCNE1 (P = 0.027) were associated with poor prognosis, while CDKN2A (P = 0.066) and E2F1 (P = 0.088) demonstrated no statistically significant differences. DISCUSSION: The study illustrates liver hepatocellular carcinoma gene signatures, related pathways and networks from the perspective of big data, featuring the cancer-specific pathway with priority, 'pathways in cancer.' The detection pool of the four highlighted genes, namely BIRC5, E2F1, CCNE1 and CDKN2A, should be further investigated given its high evidence level of diagnosis, whereas the prognostic powers of BIRC5 and CCNE1 are equally attractive and worthy of attention.

Comprehensive investigation of a novel differentially expressed lncRNA expression profile signature to assess the survival of patients with colorectal adenocarcinoma.

Growing evidence has shown that long non-coding RNAs (lncRNAs) can serve as prospective markers for survival in patients with colorectal adenocarcinoma. However, most studies have explored a limited number of lncRNAs in a small number of cases. The objective of this study is to identify a panel of lncRNA signature that could evaluate the prognosis in colorectal adenocarcinoma based on the data from The Cancer Genome Atlas (TCGA). Altogether, 371 colon adenocarcinoma (COAD) patients with complete clinical data were included in our study as the test cohort. A total of 578 differentially expressed lncRNAs (DELs) were observed, among which 20 lncRNAs closely related to overall survival (OS) in COAD patients were identified using a Cox proportional regression model. A risk score formula was developed to assess the prognostic value of the lncRNA signature in COAD with four lncRNAs (LINC01555, RP11-610P16.1, RP11-108K3.1 and LINC01207), which were identified to possess the most remarkable correlation with OS in COAD patients. COAD patients with a high-risk score had poorer OS than those with a low-risk score. The multivariate Cox regression analyses confirmed that the four-lncRNA signature could function as an independent prognostic indicator for COAD patients, which was largely mirrored in the validating cohort with rectal adenocarcinoma (READ) containing 158 cases. In addition, the correlative genes of LINC01555 and LINC01207 were enriched in the cAMP signaling and mucin type O-Glycan biosynthesis pathways. With further validation in the future, our study indicates that the four-lncRNA signature could serve as an independent biomarker for survival of colorectal adenocarcinoma.

Clinical application of fast-track surgery with Chinese medicine treatment in the devascularization operation for cirrhotic portal hypertension.

OBJECTIVE: To investigate the clinical effect of fast-track surgery combined with Chinese medicine treatment in devascularization operation for cirrhotic esophageal varices. METHODS: Seventy-two patients with cirrhotic esophageal varices were selected from January 2009 to June 2013, and randomly assigned to a conventional group and a fast-track group (fast-track surgery combined with Chinese medicine treatment) using a randomized digital table, 36 cases in each group. Operation and anesthesia recovery time, postoperative hospitalization and quality of life were recorded and compared between groups during the perioperative period. RESULTS: Compared with the conventional group, the fast-track group had longer operation time (253.6±46.4 min vs. 220.6±51.0 min) and anesthesia recovery time (50.5±15.9 min vs. 23.5±9.6 min; P<0.01); less bleeding (311.3±46.8 mL vs. 356.2±57.5 mL; P<0.01) and less transfusion (1932.3±106.9 mL vs. 2045.6±115.4 mL; P<0.01); as well as faster recovery of gastrointestinal function, shorter postoperative hospitalization and higher quality of life. There were no serious postoperative complications and no further bleeding occurred. CONCLUSION: Fast-track surgery combined with Chinese medicine treatment is a safe and feasible approach to accelerate the recovery of patients with cirrhotic portal hypertension in perioperative period of devascularization operation.

Meta-analysis of the association of glutathione S-transferase T1 null/presence gene polymorphism with the risk of gastric carcinoma.

A possible association of glutathione S-transferase T1 (GSTT1) null/presence gene polymorphism and an increased risk of developing gastric carcinoma is still unclear and hotly debated. This investigation was performed to assess the association of the GSTT1 null/presence gene polymorphism with the risk of gastric carcinoma via a meta-analysis to increase sample size and statistical significance. PubMed, Cochrane Library and CBM-disc (China Biological Medicine Database) were searched on March 1, 2013, association reports were identified, and eligible studies were recruited and synthesized. Fifty-two reports were found to be suitable for this meta-analysis for the association of the GSTT1 null genotype with gastric carcinoma risk. The results showed that there was a significantly increased gastric carcinoma risk when the GSTT1 null genotype was present in the overall population (OR 1.21, 95 % CI 1.11-1.32, P < 0.0001), Caucasians (OR 1.25, 95 % CI 1.05-1.48, P = 0.01), East-Asians (OR 1.18, 95 % CI 1.06-1.31, P = 0.003), and Chinese (OR 1.24, 95 % CI 1.07-1.44, P = 0.005). However, no statistically relevant association could be established for the Indian ethnic group (OR 1.33, 95 % CI 0.94-1.90, P = 0.11). In conclusion, the GSTT1 null genotype is associated with an increased gastric carcinoma risk in the overall population, Caucasians, East-Asians, and Chinese.

[Analysis of the effect of laparoscopic hepatectomy on 61 cases of primary liver cancer].

OBJECTIVE: To explore the feasibility and the effect of laparoscopic hepatectomy for primary liver cancer(PLC). METHODS: A retrospective study on 61 cases of laparoscopic hepatectomy for PLC was made between November 2002 and June 2007, among which there were 49 male and 12 female, aged from 14 to 71 years. All patients were diagnosed as PLC by type-B ultrasonic, CT or MRI, and APF. RESULTS: Fifty-six patients were completed laparoscopically successfully. Five cases underwent conversion to open operation because of hemorrhage. The mean operative time was 60 min (30-150 min). The mean blood loss was 450 ml (100-2000 ml). The mean hepatic portal block time was 20 min (15-30 min). All the patients had excellent recovery without any postoperative surgical complications. The patients were mobilized out of the bed in 24 hours. Oral intake of food started in 1 to 3 days. The average postoperative hospital stay was 6.6 d (5-10 d). CONCLUSION: Laparoscopic hepatectomy for PLC is safe and feasible by using hepatic portal block instrument.

[Laparoscope hepatectomy for hepatic hemangioma: a report of 18 cases].

OBJECTIVE: To evaluate the feasibility and practicality of laparoscopic hepatectomy for hepatic hemangioma. METHODS: Candidate for laparoscopic liver resection were 18 cases of hepatic hemangioma from January 2002 to October 2006. The portal bloods stream was blocked by the laparoscope portal blood blocker. The Electric-cautery and ultracision were used for liver transection. Operative procedures included anatomical left hepatectomy in 2 cases, non-anatomical left hepatectomy 1 case, left lobectomy 5 cases, local liver resection 10 cases. Two cases of hepatic hemangioma associated with gallbladder stone were performed cholecystectomy synchronously, 1 case associated with chronic appendicitis were performed appendectomy synchronously. RESULTS: Laparoscopic left liver resection was successfully performed in all 18 cases. The operative duration was (185.4 +/- 55.7) min. The quantity of blood lost during the operation was (416.2 +/- 128.8) ml. The postoperative recovery was smooth and good. No critical complications occurred. The duration for hospitalization was (6.2 +/- 1.0) d. CONCLUSION: Laparoscope hepatectomy for hepatic hemangioma is safe and feasible.

[Research progression on complement regulatory proteins CD46, CD55, and CD59 in tumor immunotherapy].

Immunologic mechanism of tumor escaping from complements' attack was unclear in the past. The efficacy of immunotherapy, especially humoral immunotherapy, to tumor is unsatisfactory. At present, with the progression in immunology, various tumors were found to highly express one or several kinds of complement regulatory proteins, such as CD46/MCP, CD55/DAF, and CD59/potectin. Complement system of the organism is inhibited because of high expression of complement regulatory proteins; therefore, the tumor can escape from the attack of complement system. Recently, the mechanism of complement regulatory proteins expressing in tumor has been studied in deep; some immunotherapies aim directly at complement regulatory proteins, including monoclonal antibody of complement regulatory proteins and cytokines, have been applied to animal experiments and clinical trails, and got some success. This review elucidated the progression on complement regulatory proteins in tumor immunotherapy.