ABSTRACT
PROPOSE: We aimed to explore the potential molecular mechanism and independent prognostic genes for colon cancer (CC). METHODS: Microarray datasets GSE17536 and GSE39582 were downloaded from Gene Expression Omnibus. Meanwhile, the whole CC-related dataset were downloaded from The Cancer Genome Atlas (TCGA) database. Differentially expressed mRNA (DEMs) were identified between cancer tissue samples and para-carcinoma tissue samples in TCGA dataset, followed by the KEGG pathway and GO function analyses. Furthermore, the clinical prognostic analysis including overall survival (OS) and disease-free survival (DFS) were performed in all three datasets. RESULTS: A total of 633 up- and 321 down-regulated mRNAs were revealed in TCGA dataset. The up-regulated mRNAs were mainly assembled in functions including extracellular matrix and pathways including Wnt signaling. The down-regulated mRNAs were mainly assembled in functions like Digestion and pathways like Drug metabolism. Furthermore, up-regulation of UL16-binding protein 2 (ULBP2) was associated with OS in CC patients. A total of 12 DEMs including Surfactant Associated 2 (SFTA2) were potential DFS prognostic genes in CC patients. Meanwhile, the GRP and Transmembrane Protein 37 (TMEM37) were two outstanding independent DFS prognostic genes in CC. CONCLUSIONS: ULBP2 might be a potential novel OS prognostic biomarker in CC, while GRP and TMEM37 could be served as the independent DFS prognostic genes in CC. Furthermore, functions including extracellular matrix and digestion, as well as pathways including Wnt signaling and drug metabolism might play important roles in the process of CC.
Subject(s)
Humans , Animals , Colonic Neoplasms/diagnosis , Colonic Neoplasms/genetics , Gene Expression Profiling/methods , RNA, Messenger/genetics , RNA, Messenger/metabolism , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Genetic Markers , Down-Regulation/genetics , Gene Expression Regulation, Neoplastic , Up-Regulation/genetics , Risk Factors , Colonic Neoplasms/metabolism , Disease-Free Survival , Gastrin-Releasing Peptide/genetics , Gastrin-Releasing Peptide/metabolism , Intercellular Signaling Peptides and Proteins/genetics , Intercellular Signaling Peptides and Proteins/metabolism , Pulmonary Surfactant-Associated Protein A/genetics , Pulmonary Surfactant-Associated Protein A/metabolism , Microarray Analysis , Murinae , Kaplan-Meier Estimate , GPI-Linked Proteins/genetics , GPI-Linked Proteins/metabolismABSTRACT
Since GABA and its related enzymes had been determined in beta-cells of pancreas islets, effects of GABA on pancreatic exocrine secretion were investigated in the isolated perfused rat pancreas. GABA, given intra-arterially at concentrations of 3, 10, 30 and 100 microM, did not exert any influence on spontaneous or secretin (12 pM)-induced pancreatic exocrine secretion. However, GABA further elevated cholecystokinin (10 pM)-, gastrin-releasing peptide (100 pM)- or electrical field stimulation-induced pancreatic secretions of fluid and amylase, dose-dependently. The GABA-enhanced CCK-induced pancreatic secretions were completely blocked by bicuculline (10 microM), a GABAA receptor antagonist but not affected by saclofen (10 microM), a GABA(B) receptor antagonist. The enhancing effects of GABA (30 microM) on CCK-induced pancreatic secretions were not changed by tetrodotoxin (1 microM) but partially reduced by cyclo-(7-aminoheptanonyl-Phe-D-Trp-Lys-Thr[BZL]) (10 microM), a somatostatin antagonist. In conclusion, GABA enhances pancreatic exocrine secretion induced by secretagogues, which stimulate enzyme secretion predominantly, via GABA(A) receptors in the rat pancreas. The enhancing effect of GABA is partially mediated by inhibition of islet somatostatin release. GABA does not modify the activity of intrapancreatic neurons.
Subject(s)
Rats , Amylases/metabolism , Animals , Baclofen/pharmacology , Baclofen/analogs & derivatives , Bicuculline/pharmacology , Cholecystokinin/metabolism , Dose-Response Relationship, Drug , Electric Stimulation , gamma-Aminobutyric Acid/pharmacology , GABA Antagonists/pharmacology , Gastrin-Releasing Peptide/metabolism , Hormones/pharmacology , In Vitro Techniques , Pancreas/metabolism , Pancreas/enzymology , Pancreas/drug effects , Receptors, GABA-A/metabolism , Secretin/metabolism , Somatostatin/pharmacology , Tetrodotoxin/pharmacologyABSTRACT
The effect of substance P (SP) on thyrotropin (TSH) secretion is controversial. In this study we evaluated the effect of SP on TSH secretion by hemipituitaries of 3-month-old Wistar rats in vitro and its interaction with gastrin-releasing peptide (GRP) at equimolar concentrations (1 µM and 10 µM). TSH release was measured under basal conditions and 30 min after incubation in the absence or presence of SP, GRP or both peptides. Pituitary TSH content was also measured in the pituitary homogenate after incubation. SP at both concentrations caused a significant (P<0.05) increase in TSH secretion compared with all other groups, which was approximately 60 percent (1 µM) and 85 percent (10 µM) higher than that of the control group (23.3 + or - 3.0 ng/ml). GRP at the lower concentration did not produce a statistically significant change in TSH secretion, whereas at the concentration of 10 µM it produced a 50 percent reduction in TSH. GRP co-incubated with substance P completely blocked the stimulatory effect of SP at both concentrations. Pituitary TSH content decreased in the SP-treated group compared to controls (0.75 + or - 0.03 µg/hemipituitary) at the same proportion as the increase in TSH secretion, and this effect was also blocked when GRP and SP were co-incubated. In conclusion, in an in vitro system, SP increased TSH secretion acting directly at the pituitary level and this effect was blocked by GRP, suggesting that GRP is more potent than SP on TSH secretion, and that this inhibitory effect could be the predominant effect in vivo