OCIAD1 promoted pancreatic ductal adenocarcinoma migration by regulating ATM.

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive neoplastic disease, characterized with poor outcomes and a 5-year survival rate less than 5%. Dysregulation or dysfunction of immune response factors contribute to cancer development. In this study, we found that OCIAD1 is high expressed in pancreatic cancer gene chip, and verified OCIAD1 associating with cancer malignancy in specimens from patients with PDAC. OCIAD1 down-regulation inhibited PDAC cell lines migration and vice versa. Further analysis of pancreatic cancer gene chip found OCIAD1 high expression was associating with low ATM expression. Then we proved that OCIAD1 regulated ATM to affect the migration of PDAC. Thus we concluded that high OCIAD1 levels in PDAC promoted tumor cells migration. OCIAD1 exerted its effects by regulating ATM.

Clinicopathologic characteristics and prognostic of gastric cancer in young patients.

OBJECTIVES: Gastric cancer (GC) in young patients is thought to exhibit a worse prognosis due to specific clinicopathologic characteristics and delayed diagnosis; however, the data are controversial. This study aimed to analyse the clinicopathologic characteristics and prognostic factors of GC in young patients and to determine whether GC is a different clinical entity in younger vs. older patients. PATIENTS AND METHODS: Clinical data of 3930 gastric cancer patients who underwent radical gastrectomy were retrospectively analysed and divided into two age groups. The younger group consisted of 342 cases of patients aged 40 years or younger at the time of surgery, and the older group included 3588 cases of patients older than 40 years. Clinicopathologic characteristics were compared using Pearson's χ(2) or Fisher's exact tests, and survival curves were constructed using the Kaplan-Meier method. RESULTS: Clinicopathologic characteristics of the younger group exhibited a predominance of females (p < 0.001), diffuse stomach lesions (p = 0.014), signet-ring cell type (p < 0.001), poorly differentiated histological tumours (p < 0.001), Borrmann type IV (p < 0.001), mixed Lauren's classification types (p = 0.004), and recurrence rate in the gastric remnant (p < 0.001). The overall 5-year survival rates in the younger group and older group were 60.8% and 53.7%, respectively (p = 0.017). When stratified by TNM stage, the younger group exhibited enhanced 5-year survival at stage IV compared with the older group (26.9% VS. 10.3%, p = 0.003). CONCLUSION: Although younger patients with GC exhibit more aggressive cancer patterns and higher recurrence rate in the gastric remnant, the overall 5-year survival rate may be better than older patients.

Different normalization strategies might cause inconsistent variation in circulating microRNAs in patients with hepatocellular carcinoma.

BACKGROUND: Circulating microRNA (miRNA) are promising biomarkers for diagnosing and prognosticating numerous diseases. Reports have demonstrated controversial or even contradictory conclusions in studies on circulating microRNA. This study aimed to evaluate the potential bias of using different reference genes for analyzing circulating microRNAs in the same malignant digestive diseases. MATERIAL AND METHODS: We measured plasma concentrations of U6-snRNA, let-7a, miRNA-21, miRNA-106a, miRNA-155, miRNA-219, miRNA-221, and miRNA-16 in patients with hepatocellular carcinoma (HCC), gastric carcinoma (GC), hepatic cirrhosis, hepatitis B, and healthy volunteers using quantitative real-time polymerase chain reaction (qPCR). The GeNorm, Normfinder, BestKeeper, and Comparative ΔCq algorithms integrated in RefFinder were used to screen the most suitable reference genes from the candidates. The 4 commonly used statistical evaluation software packages provided different results regarding the stability of the candidate reference genes. RESULTS: RefFinder revealed miRNA-106a and miRNA-21 as the most stably expressed reference genes, with comprehensive stability values of 1.189 and 1.861, respectively. U6-snRNA was the most unstable nucleic acid in our data. When 5 normalization strategies were compared using U6-snRNA, serum volume, miRNA-106a, miRNA-21, or the mean value of miRNA-106a and miRNA-21, obvious expression bias was detected in almost all target microRNAs. Intriguingly, all these normalization strategies indicated that circulating miRNA-155 is greatly upregulated in patients with HCC and GC, but downregulated in benign hepatic disease. CONCLUSIONS: Single reference genes used without justification in plasma microRNAs produce significant analysis bias or even erroneous results. Circulating miRNA-155 may be a promising non-invasive biomarker for discriminating malignant digestive tumors from the corresponding benign diseases.

Influence of ERCC1 and ERCC4 polymorphisms on response to prognosis in gastric cancer treated with FOLFOX-based chemotherapy.

Polymorphisms in the excision repair cross-complimentary group 1 (ERCC1)-excision repair cross-complimentary group 4 (ERCC4) genes have been implicated in the prognosis of various cancers. We conducted a cohort study to investigate the role of ERCC1-ERCC4 gene polymorphisms on the response to chemotherapy and the role of these two gene polymorphisms on the clinical outcomes of gastric cancer. Four hundred forty-seven patients with newly diagnosed and histopathologically confirmed primary gastric cancer were collected in our study and were followed up until March 2012. ERCC1 (rs11615, rs3212986C>A, and rs2298881) and ERCC4 (rs226466C>G, rs2276465, and rs6498486) were selected and genotyped. The overall chemotherapy response rate for treatment was 68 %. Carriers of the rs11615 TT and T allele and ERCC1 rs2298881 CC and C allele had a marginally significantly higher response rate to the chemotherapy. In the Cox proportional hazard model, the hazard ratios (HRs) for overall survival (OS) in patients carrying ERCC1 rs11615 TT genotype and T allele were 0.53 (0.29-0.95) and 0.63 (0.42-0.94), respectively. Similarly, we found a significant decreased risk of death from gastric cancer among patients carrying ERCC1 rs2298881 CC genotype and C allele when compared with CC genotype, and HRs (95% confidence interval (CI)) of OS were 0.50 (0.24-0.98) and 0.62 (0.40-0.96), respectively. Moreover, individuals carrying ERCC1 rs11615 T allele and rs2298881 C allele could decrease a 0.62-fold risk of death from gastric cancer. This study reported a carriage of ERCC1 rs11615, and rs2298881 polymorphism can be used as a predictor of response to folinic acid/5-fluorouracil (5-FU)/oxaliplatin (FOLFOX)-based chemotherapy in gastric cancer patients.

Genetic polymorphisms of XRCC1 gene and susceptibility to gastric cancer in Chinese Han population.

This study aims to evaluate whether the c.1471G > A and c.1686C > G genetic polymorphisms of XRCC1 gene influencing gastric cancer susceptibility. A total of 813 subjects with Chinese Han ethnicity were enrolled. Our data suggest that the allele and genotype frequencies are significantly different from gastric cancer patients with cancer-free controls. We find that c.1471G > A and c.1686C > G genetic polymorphisms statistically increase the risk of gastric cancer. Our findings indicate these two genetic polymorphisms are related with the susceptibility to gastric cancer, and could be used as molecular markers for detecting gastric cancer in Chinese Han ethnicity.

Efficacy and safety of tigecycline monotherapy vs. imipenem/cilastatin in Chinese patients with complicated intra-abdominal infections: a randomized controlled trial.

BACKGROUND: Tigecycline, a first-in-class broad-spectrum glycylcycline antibiotic, has broad-spectrum in vitro activity against bacteria commonly encountered in complicated intra-abdominal infections (cIAIs), including aerobic and facultative Gram-positive and Gram-negative bacteria and anaerobic bacteria. In the current trial, tigecycline was evaluated for safety and efficacy vs. imipenem/cilastatin in hospitalized Chinese patients with cIAIs. METHODS: In this phase 3, multicenter, open-label study, patients were randomly assigned to receive IV tigecycline or imipenem/cilastatin for /=1 dose of study drug and comprised the modified intent-to-treat population. In the microbiologically evaluable population, 86.5% (45 of 52) of tigecycline- and 97.9% (47 of 48) of imipenem/cilastatin-treated patients were cured at the test-of-cure assessment (12-37 days after therapy); in the microbiologic modified intent-to-treat population, cure rates were 81.7% (49 of 60) and 90.9% (50 of 55), respectively. The overall incidence of treatment-emergent adverse events was 80.4% for tigecycline vs. 53.9% after imipenem/cilastatin therapy (P < 0.001), primarily due to gastrointestinal-related events, especially nausea (21.6% vs. 3.9%; P < 0.001) and vomiting (12.4% vs. 2.0%; P = 0.005). CONCLUSIONS: Clinical cure rates for tigecycline were consistent with those found in global cIAI studies. The overall safety profile was also consistent with that observed in global studies of tigecycline for treatment of cIAI, as well as that observed in analyses of Chinese patients in those studies; no novel trends were observed. TRIAL REGISTRATION: ClinicalTrials.gov NCT00136201.

[Predictors of mortality in critically multiple trauma patients after damage control surgery].

OBJECTIVE: To investigate the efficiency of damage control surgery (DCS) and predictors of mortality in critically multiple trauma patients. METHODS: From May 1998 to February 2007, DCS were carried out in 27 patients with critically multiple trauma. Of the patients 15 cases survived (survival group) and 12 cases died (dead group). The surgical complications, causes of death, demographic, physiologic and medical parameters were collected and compared between the two groups. Multiple logistic regression analysis were performed to identify possible predictors of mortality. RESULTS: The incidence of surgical complications was 37.0 percent, and the intra-abdominal infections was the most frequent (18.5%). The overall mortality rate was 44.4 percent. The most common causes of death was multiple organ dysfunction syndrome (50.0%). With respect to predicting mortality, statistically significant differences was found in parameters as age, injury severity score (ISS), initial temperature and base excess (BE), estimated blood loss, initial ICU temperature and length of hospital stay. Older age, increased absolute value of initial BE and lower initial ICU temperature were determined as independent predictors of mortality on multiple logistic regression analysis. CONCLUSIONS: There is a comparable high morbidity and mortality rate in severely injured patients managed with DCS. Increased age, a larger absolute value of initial BE and lower initial ICU temperature could independently predict death of the patients.

[Influences of the phosphorylation of p38 mitogen activated protein kinase on gene expression of tumor necrosis factor-alpha in multiple organ dysfunction syndrome in pigs].

OBJECTIVE: To investigate that the phosphorylation of the p38 mitogen activated protein kinase (p38MAPK) influences gene expression of tumor necrosis factor-alpha (TNF-alpha) in multiple organ dysfunction syndrome (MODS) in pigs. METHODS: Thirty pigs were divided into MODS group and control group, and an animal model of MODS of "two-hit" injury, including hemorrhagic shock and endotoxemia, was reproduced. The content of p38MAPK's phosphorylation was assessed with Western blotting. TNF-alpha mRNA in peripheral blood monocytes was assayed with real time-polymerase chain reaction (RT-PCR). TNF-alpha was monitored in the peripheral blood plasma with enzyme linked immunosorbent assay (ELISA). RESULTS: Phosphorylation of p38MAPK was obviously increased in extent, which enhanced gene expression of TNF-alpha and then secretion of TNF-alpha by the peripheral blood mononuclear cell in MODS, and the differences were statistically significant compared with that of control group (P<0.05 or P<0.01). CONCLUSION: p38MAPK's phosphorylation is important in pathogenesis of MODS, and phosphorylation of p38MAPK can enhance TNF-alpha mRNA transcription and secretion of TNF-alpha from peripheral blood mononuclear cells, which is the mechanism of increased TNF-alpha in MODS.

The prevalence of Th17 cells in patients with gastric cancer.

Th17 cells have emerged as an important mediator in inflammatory and autoimmune diseases. However, recent studies suggest a potential impact of Th17 cells on tumor. The current study was designed to investigate the possible involvement of Th17 cells in gastric cancer. Compared with healthy volunteers, patients with gastric cancer had a higher proportion of Th17 cells in peripheral blood. Notably, the increased prevalence of Th17 cells was associated with clinical stage. In addition, increased populations of Th17 cells were present in tumor-draining lymph nodes with advanced disease. Furthermore, the mRNA expression levels of Th17-related factors (IL-17, IL-23p19, and RORC) in tumor tissues and the serum concentrations of IL-17 and IL-23 cytokines were significantly increased in patients with advanced gastric cancer. The results indicate that Th17 cells may contribute to gastric cancer pathogenesis.

Clinical management of abdominal trauma.

OBJECTIVE: To improve the prognosis of patients with abdominal trauma. METHODS: Between January 1993 and December 2005, 415 patients were enrolled in this research. The patients consisted of 347 males and 68 females with mean age of 36 years (ranging from 3-82 years). All abdominal traumas consisted of closed traumas (360 cases, 86.7%) and open traumas (55 cases, 13.3%). RESULTS: A total of 407 cases (98.1%) were fully recovered from trauma and the other 8 cases (1.9%) died of multiple injuries. The mean injury severity score (ISS) of all patients was 22 while the mean ISS of the patients who died in hospital was 42. Postoperative complications were seen in 9 patients such as infection of incisional wounds (6 cases), pancreatic fistula (2 cases) and intestinal fistula (1 case). All these postoperative complications were cured by the conservative treatment. CONCLUSION: Careful case history inquisition and physical examination are the basic methods to diagnose abdominal trauma. Focused abdominal ultrasonography is always the initial imaging examination because it is non-invasive and can be performed repeatedly with high accuracy. The doctors should consider the severity of local injuries and the general status of patients during the assessment of abdominal trauma. The principle of treatment is to save lives at first, then to cure the injuries. Unnecessary laparotomy should be avoided to reduce additional surgical trauma.

Characterization of long non-coding RNAs and MEF2C-AS1 identified as a novel biomarker in diffuse gastric cancer.

Previous studies proved that long noncoding RNAs (lncRNAs) play important role in human cancer. However, the knowledge of genome scale expression of lncRNAs and their potential biological function in gastric cancer is still lacking. Next generation RNA sequencing (RNA-seq) was performed on tumor tissues and matched adjacent normal tissues of six diffuse gastric cancer (DGC) patients. Then we performed a comprehensive analysis on lncRNAs and mRNA. Fifty-eight lncRNAs were upregulated and 54 lncRNAs were downregulated in diffuse gastric cancer tissue compared with adjacent tissue. The numbers of up- and downregulated mRNAs were 306 and 161, respectively. In addition, we inferred the function of lncRNAs by construction of a co-expression network for deregulated mRNAs and lncRNAs. Co-expressed genes of MEF2C-AS1 and FENDRR were enriched to RAS and TGF-beta signaling pathway. MEF2C-AS1 and FENDRR expression were re-evaluated by Real-time Quantitative PCR in 42 DGC patients' tumor and normal tissues, and other 46 DGC patents' and 21 healthy controls' plasma. Validation data showed MEF2C-AS1 and FENDRR were significantly downregulated in tumor tissues compared with normal tissues. And decreased FENDRR are associated with aggressive tumor characteristics including more advanced stage (P = .030), poor differentiation (P = .043) and lymphatic metastasis (P = .001). The expression level MEF2C-AS1 was significantly lower in DGC patients' plasma than that in healthy controls' plasma. In gastric cancer cell lines, knock-down of MEF2C-AS1 or FENDRR reduced the protein levels of FAT3, NTN1 and LYVE1 (the co-expressed genes), which were related with gastric cancer cell proliferation and invasion by previous studies. In addition, knock-down of MEF2C-AS1 or FENDRR promoted aggressive tumor behaviors in in-vitro assays. In this study, we provide a valuable resource of lncRNAs which might play important roles in the function of oncogenes or tumor suppressors affecting the development and progression of diffuse gastric cancer.

Enhanced recovery after surgery decreases intestinal recovery time and pain intensity in patients undergoing curative gastrectomy.

BACKGROUND: Enhanced recovery after surgery (ERAS) reduces postoperative stress, increases patient satisfaction, and reduces postoperative stay and cost. In this study, we evaluated the feasibility and effectiveness of ERAS protocols compared with conventional perioperative care group and their effect in gastric cancer patients undergoing gastrectomy. METHODS: A cohort of 366 patients were analyzed from a prospectively maintained database. The patients' characteristics, tumor profile, surgical information data and postoperative complications were evaluated. RESULTS: Patients in the ERAS had a faster gastrointestinal function recovery and first flatus (3.26±0.64; P<0.001). Pain intensity of patients in the ERAS group was significantly lower than that of patients in the conventional care group on postoperative days 1 (2.33±0.98; P<0.001) and 3 (1.06±0.63; P<0.001). Postoperative hospital stays were significantly shorter in patients receiving ERAS program (6.66±3.36; P<0.001), than in those patients who received conventional perioperative care (9.02±2.61). CONCLUSION: ERAS can reduce postoperative stress, enhance the recovery of the gut, reduce the pain intensity, and increase satisfaction in gastric cancer patient undergoing curative gastrectomy.

Plasma olfactomedin 4 level in peripheral blood and its association with clinical features of breast cancer.

The present study aimed to investigate the expression of olfactomedin 4 (OLFM4) in plasma of patients with breast cancer and its association with diagnosis, metastasis and prognosis of breast cancer. OLFM4 gene expression level of peripheral blood plasma in 60 patients with breast cancer and 26 healthy donors was examined by ELISA. The expression of OLFM4 in tumor tissues of patients with breast cancer was evaluated by immunohistochemistry (protein expression) and reverse transcription-quantitative polymerase chain reaction (mRNA expression), respectively. Circulating tumor cells (CTCs) were detected in a certain set of patients. The expression of OLFM4 in plasma of the overall healthy people was higher compared with patients with breast cancer. The plasma OLFM4 level in patients with breast cancer was consistent with the expression of OLFM4 protein in tumor tissues (R2=1), indicating that the level of plasma OLFM4 expression may represent the expression of OLFM4 in breast cancer tissues. The plasma OLFM4 level in patients with histological grade I was significantly lower compared with grade III (P<0.05). Breast cancer patients with positive CTC were associated with low level of plasma OLFM4. These results suggest that low OLFM4 expression in plasma or tissue specimens of breast cancer patients is more likely to represent low histological differentiation and decreased invasive/metastatic capabilities. Taken together, plasma OLFM4 level may be considered as a biomarker for diagnosis and prognosis of breast cancer for cases where there are difficulties in obtaining tumor tissue samples.

Downregulation of Notch-regulated Ankyrin Repeat Protein Exerts Antitumor Activities against Growth of Thyroid Cancer.

BACKGROUND: The Notch-regulated ankyrin repeat protein (NRARP) is recently found to promote proliferation of breast cancer cells. The role of NRARP in carcinogenesis deserves extensive investigations. This study attempted to investigate the expression of NRARP in thyroid cancer tissues and assess the influence of NRARP on cell proliferation, apoptosis, cell cycle, and invasion in thyroid cancer. METHODS: Thirty-four cases with thyroid cancer were collected from the Department of General Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine between 2011 and 2012. Immunohistochemistry was used to detect the level of NRARP in cancer tissues. Lentivirus carrying NRARP-shRNA (Lenti-NRARP-shRNA) was applied to down-regulate NRARP expression. Cell viability was tested after treatment with Lenti-NRARP-shRNA using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Apoptosis and cell cycle distribution were determined by flow cytometry. Cell invasion was tested using Transwell invasion assay. In addition, expressions of several cell cycle-associated and apoptosis-associated proteins were examined using Western blotting after transfection. Student's t-test, one-way analysis of variance (ANOVA), or Kaplan-Meier were used to analyze the differences between two group or three groups. RESULTS: NRARP was highly expressed in thyroid cancer tissues. Lenti-NRARP-shRNA showed significantly inhibitory activities against cell growth at a multiplicity of infection of 10 or higher (P < 0.05). Lenti-NRARP-shRNA-induced G1 arrest (BHT101: 72.57% ± 5.32%; 8305C: 75.45% ± 5.26%) by promoting p21 expression, induced apoptosis by promoting bax expression and suppressing bcl-2 expression, and inhibited cell invasion by suppressing matrix metalloproteinase-9 expression. CONCLUSION: Downregulation of NRARP expression exerts significant antitumor activities against cell growth and invasion of thyroid cancer, that suggests a potential role of NRARP in thyroid cancer targeted therapy.

Long-term complications requiring reoperations after laparoscopic adjustable gastric banding: a systematic review.

At present, bariatric surgery is the most effective option for morbidly obese patients. Among all of the surgical procedures, laparoscopic adjustable gastric banding (LAGB) is characterized by superior safety, a stable weight loss effect, and unique reversibility. However, the worldwide popularity of LAGB is challenged and overshadowed by a number of adverse events. This systematic review examined the incidence and outcomes of the long-term complications that require reoperations after LAGB. A PubMed search was conducted through October 31, 2014, for relevant studies that included minimal 10-year follow-up data for LAGB patients. The defined outcomes of interest were weight loss outcomes, long-term complications, and reoperations. Seventeen studies, including 2 randomized controlled trials and 15 observational studies, were identified involving a total of 9706 LAGB patients, of which 8215 patients (84.6%) were followed up and 1974 patients (20.3%) were available 10 years after LAGB. The follow-up data indicated that the mean percentage of excess weight loss at 10 years after LAGB was 49.1% ± 13.1% and the median long-term complication rate and reoperation rate for the LAGB patients were 42.7% (5.9%-52.9%) and 36.5% (7.2%-66.1%), respectively. At the end of long-term follow-up, approximately 22.9% (5.4%-54.0%) of the LAGB patients had their bands removed and the commonest reason was complications. In conclusion, long-term adverse events are important and remarkable for LAGB patients. The role of LAGB in bariatric surgery is worthy of further appraisal, by comparing with other types of bariatric procedures, because of the limited high-quality evidence.

EFFECTS OF HELIUM PRECONDITIONING ON INTESTINAL ISCHEMIA AND REPERFUSION INJURY IN RATS.

Intestinal ischemia-reperfusion (I/R) injury can occur in clinical settings such as organ transplantation, cardiopulmonary bypass and trauma. The noble gas helium attenuates I/R injury in a number of animal organs and thus may offer a strategy for reducing I/R-induced intestinal injury in clinical settings. In the present study, we used four different helium preconditioning (HPC) profiles to investigate the potential beneficial effect of HPC on I/R-induced intestinal injury. Male Sprague-Dawley rats were pretreated with three cycles of air breathing for 5 min combined with three cycles of breathing a 70% helium:30% oxygen mixture for either 2, 5, 10, or 15 min, after which they were subjected to 60-min intestinal ischemia and 60-min reperfusion. Sixty minutes after reperfusion, the intestinal tissues of the variously treated rats were analyzed using histology, immunohistochemistry, terminal dUTP nick-end labeling staining, myeloperoxidase activity assay, Western blotting, and enzyme-linked immunosorbent assay for tumor necrosis factor α and macrophage inflammatory protein 1α. Intestinal permeability was assayed by measuring fluorescein isothiocyanate-dextran release in blood samples. The results showed that the HPC profile consisting of three cycles of 10 or 15 min of helium breathing and three cycles of 5 min of air breathing reduced I/R-induced intestinal injury, cell apoptosis, and the inflammatory response. However, the 2- or 5-min helium breathing did not confer any protective effects. It seems that longer helium episodes should be used in HPC profiles designed to attenuate intestinal I/R injury.

TSPAN1 functions as an oncogene in gastric cancer and is downregulated by miR-573.

Tetraspanin 1 (TSPAN1) has been reported to be upregulated in gastric cancer (GC). However, whilst TSPAN1 is positively correlated with clinical stage and negatively correlated with survival rates, its function in GC remains elusive. Here we show that expression of TSPAN1 is significantly higher in GC tissues compared to non-cancerous tissues. Furthermore, we demonstrate that RNAi-mediated down-regulation of TSPAN1 expression markedly blocks GC cell proliferation, cell cycle progression and invasive activity. We identified TSPAN1 as a novel target gene of miR-573. Overexpression of miR-573 suppressed proliferation and invasion of GC cells by down-regulation of TSPAN1 expression. Restoration of TSPAN1 rescued the effects of miR-573 overexpression. Therefore, our findings suggest that the miR-573/TSPAN1 axis is important in the control of gastric carcinogenesis.

Caveolin-1 is a modulator of fibroblast activation and a potential biomarker for gastric cancer.

Stromal fibroblasts play an important role in chronic cancer-related inflammation and the development as well as progression of malignant diseases. However, the difference and relationship between inflammation-associated fibroblasts (IAFs) and cancer-associated fibroblasts (CAFs) are poorly understood. In this study, gastric cancer-associated fibroblasts (GCAFs) and their corresponding inflammation-associated fibroblasts (GIAFs) were isolated from gastric cancer (GC) with chronic gastritis and cultured in vitro. These activated fibroblasts exhibited distinct secretion and tumor-promoting behaviors in vitro. Using proteomics and bioinformatics techniques, caveolin-1 (Cav-1) was identified as a major network-centric protein of a sub-network consisting of 121 differentially expressed proteins between GIAFs and GCAFs. Furthermore, immunohistochemistry in a GC cohort showed significant difference in Cav-1 expression score between GIAFs and GCAFs and among patients with different grades of chronic gastritis. Moreover, silencing of Cav-1 in GIAFs and GCAFs using small interfering RNA increased the production of pro-inflammatory and tumor-enhancing cytokines and chemokines in conditioned mediums that elevated cell proliferation and migration when added to GC cell lines AGS and MKN45 in vitro. In addition, Cav-1 status in GIAFs and GCAFs independently predicted the prognosis of GC. Our findings indicate that Cav-1 loss contributes to the distinct activation statuses of fibroblasts in GC microenvironment and gastritis mucosa, and Cav-1 expression in both GCAFs and GIAFs may serve as a potential biomarker for GC progression.

Long non-coding RNA GHET1 promotes gastric carcinoma cell proliferation by increasing c-Myc mRNA stability.

Long non-coding RNAs (lncRNAs), a recently characterized class of non-coding RNAs, have been shown to have important regulatory roles and are de-regulated in a variety of tumors. However, the contributions of lncRNAs to gastric carcinoma and their functional mechanisms remain largely unknown. In this study, we found that lncRNA gastric carcinoma high expressed transcript 1 (lncRNA-GHET1) was up-regulated in gastric carcinoma. The over-expression of this lncRNA correlates with tumor size, tumor invasion and poor survival. Gain-of-function and loss-of-function analyses demonstrated that GHET1 over-expression promotes the proliferation of gastric carcinoma cells in vitro and in vivo. Knockdown of GHET1 inhibits the proliferation of gastric carcinoma cells. RNA pull-down and immunoprecipitation assays confirmed that GHET1 physically associates with insulin-like growth factor 2 mRNA binding protein 1 (IGF2BP1) and enhances the physical interaction between c-Myc mRNA and IGF2BP1, consequently increasing the stability of c-Myc mRNA and expression. The expression of GHET1 and c-Myc is strongly correlated in gastric carcinoma tissues. Depletion of c-Myc abolishes the effects of GHET1 on proliferation of gastric carcinoma cells. Taken together, these findings indicate that GHET1 plays a pivotal role in gastric carcinoma cell proliferation via increasing c-Myc mRNA stability and expression, which suggests potential use of GHET1 for the prognosis and treatment of gastric carcinoma.

Functional polymorphisms of circadian negative feedback regulation genes are associated with clinical outcome in hepatocellular carcinoma patients receiving radical resection.

Previous studies have demonstrated that circadian negative feedback loop genes play an important role in the development and progression of many cancers. However, the associations between single-nucleotide polymorphisms (SNPs) in these genes and the clinical outcomes of hepatocellular carcinoma (HCC) after surgical resection have not been studied so far. Thirteen functional SNPs in circadian genes were genotyped using the Sequenom iPLEX genotyping system in a cohort of 489 Chinese HCC patients who received radical resection. Multivariate Cox proportional hazards model and Kaplan-Meier curve were used for the prognosis analysis. Cumulative effect analysis and survival tree analysis were used for the multiple SNPs analysis. Four individual SNPs, including rs3027178 in PER1, rs228669 and rs2640908 in PER3 and rs3809236 in CRY1, were significantly associated with overall survival (OS) of HCC patients, and three SNPs, including rs3027178 in PER1, rs228729 in PER3 and rs3809236 in CRY1, were significantly associated with recurrence-free survival (RFS). Moreover, we observed a cumulative effect of significant SNPs on OS and RFS (P for trend < 0.001 for both). Survival tree analysis indicated that wild genotype of rs228729 in PER3 was the primary risk factor contributing to HCC patients' RFS. Our study suggests that the polymorphisms in circadian negative feedback loop genes may serve as independent prognostic biomarkers in predicting clinical outcomes for HCC patients who received radical resection. Further studies with different ethnicities are needed to validate our findings and generalize its clinical utility.