ABSTRACT
BACKGROUND: Pancreatic cancer is a highly lethal disease with a poor prognosis while metformin has been associated with a decreased risk of pancreatic cancer. Although the benefit of metformin was observed for pancreatic cancer prevention, it is not clear whether it can also affect the survival of pancreatic cancer patients with type 2 diabetes mellitus. A systematic review and meta-analysis was conducted to assess the effect of metformin on the survival of pancreatic cancer patients with type 2 diabetes mellitus. METHODS: Two independent authors searched PubMed and Web of science up to 08/07/2016. We assessed studies for eligibility, extracted data, and examined their quality, with the primary outcome as overall survival. We used published hazard ratio (HR) available or estimated based on other survival data. We pooled the data and used a random-effect model to combine direct comparisons from included articles. We also investigated treatment effects by different countries, quality and the time of metformin initiation. RESULTS: We found that there was a relative survival benefit associated with metformin treatment compared with non-metformin treatment in both overall survival (OS) ([HR] 0.84; 95% confidence interval [CI]: 0.73 - 0.96). These associations were also observed in subgroups of Asian countries and high quality articles. CONCLUSIONS: Our results support the notion that metformin maybe the best anti-diabetic medicine of choice in patients with pancreatic cancer and concurrent type 2 diabetes mellitus. The perspectives of enhancing survival of pancreatic cancer patients with diabetes mellitus by the use of metformin deserve more attention in future research and clinical practice.
Subject(s)
Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/drug therapy , Hypoglycemic Agents/therapeutic use , Metformin/therapeutic use , Pancreatic Neoplasms/complications , Pancreatic Neoplasms/mortality , Humans , Proportional Hazards Models , Publication BiasABSTRACT
Pancreatic cancer (PC) has a high mortality rate because it is usually diagnosed late. Glycosylation of proteins is known to change in tumor cells during the development of PC. The objectives of this study were to identify and validate the diagnostic value of novel biomarkers based on N-glycomic profiling for PC. In total, 217 individuals including subjects with PC, pancreatitis, and healthy controls were divided randomly into a training group (n = 164) and validation groups (n = 53). Serum N-glycomic profiling was analyzed by DSA-FACE. The diagnostic model was constructed based on N-glycan markers with logistic stepwise regression. The diagnostic performance of the model was assessed further in validation cohort. The level of total core fucose residues was increased significantly in PC. Two diagnostic models designated GlycoPCtest and PCmodel (combining GlycoPCtest and CA19-9) were constructed to differentiate PC from normal. The area under the receiver operating characteristic curve (AUC) of PCmodel was higher than that of CA19-9 (0.925 vs. 0.878). The diagnostic models based on N-glycans are new, valuable, noninvasive alternatives for identifying PC. The diagnostic efficacy is improved by combined GlycoPCtest and CA19-9 for the discrimination of patients with PC from healthy controls.
Subject(s)
Biomarkers, Tumor/blood , CA-19-9 Antigen/blood , Neoplasm Proteins/blood , Pancreatic Neoplasms/diagnosis , Pancreatitis/diagnosis , Polysaccharides/blood , Adult , Aged , Area Under Curve , Biomarkers, Tumor/genetics , CA-19-9 Antigen/genetics , Carbohydrate Sequence , Case-Control Studies , Diagnosis, Differential , Female , Glycomics/methods , Glycosylation , Humans , Logistic Models , Male , Middle Aged , Neoplasm Proteins/genetics , Pancreatic Neoplasms/blood , Pancreatic Neoplasms/genetics , Pancreatic Neoplasms/pathology , Pancreatitis/blood , Pancreatitis/genetics , Pancreatitis/pathology , Polysaccharides/chemistry , ROC Curve , Pancreatic NeoplasmsABSTRACT
The oxyguanine glycosylase 1 (OGG1) gene has an important role in DNA repair, and the polymorphism of the gene may alter cancer susceptibility. This study aims to examine the association between the OGG1 Ser326Cys polymorphism and cancer risk based on meta-analysis. Relevant studies were identified through a search of PubMed and Weipu databases, and a total of 109 studies including 111 comparisons containing 34,041 cases and 42,730 controls were enrolled. Overall, significant association was observed between OGG1 Ser326Cys polymorphism and cancer risk in all genetic models except for heterozygote model (Cys/Cys + Cys/Ser vs Ser/Ser: OR 1.071, 95 % CI 1.019-1.125; Cys/Cys vs Cys/Ser + Ser/Ser: OR 1.159, 95 % CI 1.076-1.248; Cys/Cys vs Ser/Ser: OR 1.202, 95 % CI 1.105-1.308). In stratified analysis by cancer type, significantly increased cancer risk was observed in digestive system cancer, head and neck cancer and lung cancer. For gynecologic cancer, significantly increased cancer risk was also observed in homozygote model (OR 1.974, 95 % CI 1.254-3.107). In addition, in stratified analysis by ethnicities, increased cancer risk was found in Asians (Cys/Cys vs Cys/Ser + Ser/Ser: OR 1.195, 95 % CI 1.088-1.313; Cys/Cys + Cys/Ser vs Ser/Ser: OR 1.115, 95 % CI 1.045-1.190; Cys/Cys vs Ser/Ser: OR 1.273, 95 % CI 1.149-1.410). The OGG1 Ser326Cys polymorphism may be a risk factor for cancers of lung, digestive system and head and neck.
Subject(s)
DNA Glycosylases/genetics , Genetic Predisposition to Disease/genetics , Neoplasms/genetics , Polymorphism, Single Nucleotide , Genotype , HumansABSTRACT
The object of the study is to identify N-glycan profiling changes associated with gastric cancer and explore the impact of core-fucosylation on biological behaviors of human gastric cancer cells. A total of 244 subjects including gastric cancer, gastric ulcer and healthy control were recruited. N-glycan profiling from serum and total proteins in gastric tissues was analyzed by DNA sequencer-assisted fluorophore-assisted capillary electrophoresis. The abundance of total core-fucosylated residues and the expression of enzymes involved in core-fucosylation were analyzed with lectin blot, quantitative reverse transcription-polymerase chain reaction, western blot, Immunohistochemical staining and lectin-histochemical staining. The recombinant plasmids of GDP-fucose transporter and α-1,6-fucosyltransferase (Fut8) were constructed and transfected into gastric cancer cell lines BGC-823 and SGC-7901. CCK-8 and wound healing assay were used to assess the functional impact of core-fucosylation modulation on cell proliferation and migration. Characteristic serum N-glycan profiles were found in gastric cancer. Compared with the healthy control, a trianntenary structure abundance, peak 9 (NA3Fb), was increased significantly in gastric cancer, while the total abundance of core-fucosylated residues (sumfuc) was decreased. Core-fucosylated structures, peak6(NA2F) and peak7(NA2FB) were deceased in gastric tumor tissues when compared with that in adjacent non-tumor tissues. Consistently, lens culinaris agglutinin (LCA)-binding proteins were decreased significantly in sera of gastric cancer, and protein level of Fut8 was decreased significantly in gastric tumor tissues compared with that in adjacent non-tumor tissues. Upregulation of GDP-Tr and Fut8 could inhibit proliferation, but had no significant influence on migration of BGC-823 and SGC-7901 cells. Core-fucosylation is down regulated in gastric cancer. Upregulation of core-fucosylation could inhibit proliferation of the human gastric cancer cells.
