Identification of TPD52 and DNAJB1 as two novel bile biomarkers for cholangiocarcinoma by iTRAQ­based quantitative proteomics analysis.

Cholangiocarcinoma (CCA) represents a type of epithelial cancer with a late diagnosis and poor outcome. However, the molecular mechanisms responsible for the development of CCA have not yet been fully identified. Thus, in this study, we aimed to elucidate some of these mechanisms. For this purpose, isobaric tags for relative and absolute quantification (iTRAQ) was performed to analyze the secretory proteins from the 2 CCA cell lines, TFK1 and HuCCT1, as well as from a normal biliary epithelial cell line, human intrahepatic biliary epithelial cells (HiBECs). Differentially expressed proteins (DEPs) were identified and biological process analysis was performed according to the Gene Ontology (GO) functional classification annotation and KEGG metabolic pathway map analysis. tumor protein D52 (TPD52) and DnaJ heat shock protein family (Hsp40) member B1 (DNAJB1) were validated using RT­qPCR, western blot analysis and immunohistochemistry. In total, 778 proteins were identified as DEPs. Following validation, TPD52 and DNAJB1 were used for further analysis. The expression levels of TPD52 and DNAJB1 were elevated in CCA cell lines, tissues and bile samples, suggesting that these proteins may contribute to tumor pathogenesis. In addition, the expression levels of TPD52 and DNAJB1 were found to be closely associated with the clinical parameters and prognosis of patients with CCA. On the whole, the findings of this study indicate that TPD52 and DNAJB1 may serve as novel bile biomarkers for CCA.

Risk factors for neck hematoma requiring surgical re-intervention after thyroidectomy: a systematic review and meta-analysis.

BACKGROUND: In this systematic review and meta-analysis, we aimed to determine the risk factors associated with neck hematoma requiring surgical re-intervention after thyroidectomy. METHODS: We systematically searched all articles available in the literature published in PubMed and CNKI databases through May 30, 2017. The quality of these articles was assessed using the Newcastle-Ottawa Quality Assessment Scale, and data were extracted for classification and analysis by focusing on articles related with neck hematoma requiring surgical re-intervention after thyroidectomy. Our meta-analysis was performed according to the Preferred Reporting Items for Systematic Review and Meta-Analyses guidelines. RESULTS: Of the 1028 screened articles, 26 met the inclusion criteria and were finally analyzed. The factors associated with a high risk of neck hematoma requiring surgical re-intervention after thyroidectomy included male gender (odds ratio [OR]: 1.86, 95% confidence interval [CI]: 1.60-2.17, P < 0.00001), age (MD: 4.92, 95% CI: 4.28-5.56, P < 0.00001), Graves disease (OR: 1.81, 95% CI: 1.60-2.05, P < 0.00001), hypertension (OR: 2.27, 95% CI: 1.43-3.60, P = 0.0005), antithrombotic drug use (OR: 1.92, 95% CI: 1.51-2.44, P < 0.00001), thyroid procedure in low-volume hospitals (OR: 1.32, 95% CI: 1.12-1.57, P = 0.001), prior thyroid surgery (OR: 1.93, 95% CI: 1.11-3.37, P = 0.02), bilateral thyroidectomy (OR: 1.19, 95% CI: 1.09-1.30, P < 0.0001), and neck dissection (OR: 1.55, 95% CI: 1.23-1.94, P = 0.0002). Smoking status (OR: 1.19, 95% CI: 0.99-1.42, P = 0.06), malignant tumors (OR: 1.00, 95% CI: 0.83-1.20, P = 0.97), and drainage used (OR: 2.02, 95% CI: 0.69-5.89, P = 0.20) were not significantly associated with postoperative neck hematoma. CONCLUSION: We identified certain risk factors for neck hematoma requiring surgical re-intervention after thyroidectomy, including male gender, age, Graves disease, hypertension, antithrombotic agent use, history of thyroid procedures in low-volume hospitals, previous thyroid surgery, bilateral thyroidectomy, and neck dissection. Appropriate intervention measures based on these risk factors may reduce the incidence of postoperative hematoma and yield greater benefits for the patients.

Roles of Cyclooxygenase-2 gene -765G > C (rs20417) and -1195G > A (rs689466) polymorphisms in gastric cancer: A systematic review and meta-analysis.

BACKGROUND: The roles of cyclooxygenase-2 (COX2) -765G > C (rs20417) and -1195G > A (rs689466) polymorphisms in gastric cancer were intensively analyzed, but the results of these studies were inconsistent. We conducted a meta-analysis and trial sequential analysis to elucidate the associations between these two COX2 polymorphisms and gastric cancer risk. METHODS: Eligible studies were searched in PubMed, Embase, Cochrane library databases, China National Knowledge Infrastructure, Vip, and Wanfang databases. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the genetic correlation between COX2 polymorphisms and gastric cancer susceptibility in five genetic models. Trial sequential analysis (TSA) was conducted to estimate whether the evidence of the results is sufficient. Furthermore, their interactions with Helicobacter pylori (H. pylori) or smoking in gastric cancer were also assessed using a case-only method. RESULTS: The COX2 gene -765G > C polymorphism showed no significant association with gastric cancer susceptibility under all the five genetic models (take the allelic model for example: OR = 1.41, 95% CI: 0.95-2.09) in total analysis, and the stratification analysis by ethnicity indicated a similar association in Caucasian group under four genetic models (allelic model, dominant model, homozygous model, and heterozygous model). But in the subgroup of the Asian population, the -765G > C polymorphism was significantly associated with gastric cancer risk under the same contrast. The COX2 -1195G > A polymorphism showed significant correlation with gastric cancer susceptibility in total analysis, and stratification analysis by ethnicity also revealed a similar association in both Asian and Caucasian groups under the same contrast. Moreover, TSA confirmed such associations. Both H. pylori infection and cigarette smoking interacted with -765 C allele in gastric cancer (OR = 3.79, 95% CI: 1.15-12.43 and OR = 2.48, 95% CI: 1.38-4.48, respectively), but not in -1195 A allele (OR = 1.96, 95% CI: 0.62-6.21, and OR = 1.24, 95% CI: 0.93-1.64, respectively). CONCLUSIONS: COX2 -765G > C polymorphism may serve as a genetic biomarker of gastric cancer in Asians, but not in Caucasians. COX2 -1195G > A polymorphism may serve as a genetic biomarker of gastric cancer in both Asians and Caucasians. The -765G > C, rather than -1195G > A polymorphism interacted with H. pylori infection or cigarette smoking to increase gastric cancer risk.

Comparison of DWI and 18F-FDG PET/CT for assessing preoperative N-staging in gastric cancer: evidence from a meta-analysis.

The diagnostic values of diffusion weighted imaging (DWI) and 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) for N-staging of gastric cancer (GC) were identified and compared. After a systematic search to identify relevant articles, meta-analysis was used to summarize the sensitivities, specificities, and areas under curves (AUCs) for DWI and PET/CT. To better understand the diagnostic utility of DWI and PET/CT for N-staging, the performance of multi-detector computed tomography (MDCT) was used as a reference. Fifteen studies were analyzed. The pooled sensitivity, specificity, and AUC with 95% confidence intervals of DWI were 0.79 (0.73-0.85), 0.69 (0.61-0.77), and 0.81 (0.77-0.84), respectively. For PET/CT, the corresponding values were 0.52 (0.39-0.64), 0.88 (0.61-0.97), and 0.66 (0.62-0.70), respectively. Comparison of the two techniques revealed DWI had higher sensitivity and AUC, but no difference in specificity. DWI exhibited higher sensitivity but lower specificity than MDCT, and 18F-FDG PET/CT had lower sensitivity and equivalent specificity. Overall, DWI performed better than 18F-FDG PET/CT for preoperative N-staging in GC. When the efficacy of MDCT was taken as a reference, DWI represented a complementary imaging technique, while 18F-FDG PET/CT had limited utility for preoperative N-staging.

Value and impact factors of multidetector computed tomography in diagnosis of preoperative lymph node metastasis in gastric cancer: A PRISMA-compliant systematic review and meta-analysis.

BACKGROUND: Multidetector computed tomography (MDCT) exhibited wide ranges of sensitivities and specificities for lymph node assessment of gastric cancer (GC) in several individual studies. This present meta-analysis was carried out to evaluate the value of MDCT in diagnosis of preoperative lymph node metastasis (LNM) and to explore the impact factors that might explain the heterogeneity of its diagnostic accuracy in GC. METHODS: A comprehensive search was conducted to collect all the relevant studies about the value of MDCT in assessing LNM of GC within the PubMed, Cochrane library and Embase databases up to Feb 2, 2016. Two investigators independently screened the studies, extracted data, and evaluated the quality of included studies. The sensitivity, specificity, and area under ROC curve (AUC) were pooled to estimate the overall accuracy of MDCT. Meta-regression and subgroup analysis were carried out to identify the possible factors influencing the heterogeneity of the accuracy. RESULTS: A total of 27 studies with 6519 subjects were finally included. Overall, the pooled sensitivity, specificity, and AUC were 0.67 (95% CI: 0.56-0.77), 0.86 (95% CI: 0.81-0.90), and 0.86 (95% CI: 0.83-0.89), respectively. Meta-regression revealed that MDCT section thickness, proportion of serosal invasion, and publication year were the main significant impact factors in sensitivity, and MDCT section thickness, multiplanar reformation (MPR), and reference standard were the main significant impact factors in specificity. After the included studies were divided into 2 groups (Group A: studies with proportion of serosa-invasive GC subjects ≥50%; Group B: studies with proportion of serosa-invasive GC subjects <50%), the pooled sensitivity in Group A was significantly higher than in Group B (0.84 [95% CI: 0.75-0.90] vs 0.55 [95% CI: 0.41-0.68], P < .01). For early gastric cancer (EGC), the pooled sensitivity, specificity, and AUC were 0.34 (95% CI: 0.15-0.61), 0.91 (95% CI: 0.84-0.95), and 0.83 (95% CI: 0.80-0.86), respectively. CONCLUSION: To summarize, MDCT tends to be adequate to assess preoperative LNM in serosa-invasive GC, but insufficient for non-serosa-invasive GC (particularly for EGC) owing to its low sensitivity. Proportion of serosa-invasive GC subjects, MDCT section thickness, MPR, and reference standard are the main factors influencing its diagnostic accuracy.

Correlation Between Interleukin-1ß-511 C/T Polymorphism and Gastric Cancer in Chinese Populations: A Meta-Analysis.

BACKGROUND Several studies have indicated that interleukin (IL)-1ß-511 C/T polymorphism may contribute to individual susceptibility to gastric cancer, but the results vary among regions and races. No relevant meta-analysis has been conducted in a Chinese population. Therefore, we performed the current meta-analysis to investigate the possible correlation between IL-1ß-511 C/T polymorphism and gastric cancer susceptibility in Chinese subjects. MATERIAL AND METHODS PubMed, EmBase, Cochrane Library, Chinese Biology Medicine (CBM), Chinese National Knowledge Infrastructure (CNKI), and Wanfang databases were searched for case-control studies published before 21 January 2015 and investigating a correlation between IL-1ß-511 C/T polymorphism and gastric cancer susceptibility. Two investigators independently screened the studies, extracted data, and evaluated the quality of included studies with the Newcastle-Ottawa scale. Meta-analysis was conducted with STATA 12.0. RESULTS A total of 27 articles from 28 case-control studies were collected. Meta-analysis showed that IL-1ß-511C/T polymorphism was related to increased susceptibility to gastric cancer in Chinese subjects [T vs. C: OR=1.21, 95%CI (1.07-1.37), P<0.01; TT vs. CC: OR=1.41, 95%CI (1.11-1.80), P<0.01; CT vs. CC: OR=1.26, 95% CI (1.05-1.50), P<0.01; TT+CT vs. CC: OR=1.31, 95%CI (1.08-1.58), P<0.01; and TT vs. CT+CC: OR=1.24, 95%CI (1.05-1.47), P<0.01]. Subgroup analysis showed a significant correlation between IL-1ß-511C/T polymorphism and susceptibility to gastric cancer in residents of southern China and in patients with intestinal-type gastric cancer, but not in residents of northern China or in patients with diffuse gastric cancer. Moreover, H. pylori-infected subjects carrying T (CT+TT) exhibited a relatively higher risk of GC [OR=2.4, 95% CI (1.2-5.1), P=0.02]. CONCLUSIONS IL-1ß-511C/T polymorphism is significantly associated with increased susceptibility to gastric cancer in residents of southern China and in intestinal-type gastric cancer. We also found a synergistic interaction between IL-1ß-511C/T polymorphism and H. pylori infection in the development of GC.

Efficient isolation and proteomic analysis of cell plasma membrane proteins in gastric cancer reveal a novel differentiation and progression related cell surface marker, R-cadherin.

Cell plasma membrane proteins, playing a crucial role in cell malignant transformation and development, were the main targets of tumor detection and therapy. In this study, CyDye/biotin double-labeling proteomic approach was adopted to profile the membrane proteome of gastric cancer cell line BGC-823 and paired immortalized gastric epithelial cell GES-1. Real-time PCR, Western blotting, and immunohistochemical staining were used to validate the differential expression of a novel identified cell surface marker R-cadherin in gastric cancer cells and tissues. Clinicopathological study and survival analysis were performed to estimate its roles in tumor progression and outcome prediction. Real-time PCR and Western blotting showed that the expression level of R-cadherin in gastric cancer were significantly lower than non-cancerous epithelial cell and tissues. Clinicopathological study indicated that R-cadherin was dominantly expressed on cell surface of normal gastric epithelium, and its expression deletion in gastric cancer tissues was associated with tumor site, differentiation, lymph node metastasis, and pTNM (chi-square test, P < 0.05). Those patients with R-cadherin positive expression displayed better overall survivals than negative expression group (log-rank test, P = 0.000). Cox multivariate survival analysis revealed lacking the expression of R-cadherin was a main independent predictor for poor clinical outcome in gastric cancer (RR = 5.680, 95 % CI 2.250-14.341, P < 0.01). We have established a fundamental membrane proteome database for gastric cancer and identified R-cadherin as a tumor differentiation and progression-related cell surface marker of gastric cancer. Lacking the expression of R-cadherin indicates poor prognosis in patients with gastric cancer.