Interleukin-10 (IL10), a pleiotropic cytokine secreted by type-2 helper (Th2) T cells, contributes to the oncogenic activation or inactivation of tumor-suppressor genes. The present study investigated whether hypomethylation of IL10 CpG island (CGI) was associated with the risk of developing gastric cancer (GC) and the prognosis of patients with GC. A fragment (hg18, chr1: 206945638-206945774) at the CGI of IL10 was selected for the present methylation assay. Quantitative methylation-specific PCR was used to evaluate the methylation of IL10 CGI in 117 tumor samples from patients with GC. The results demonstrated that IL10 CGI methylation was significantly lower in the tumor tissues compared with that in the paired adjacent non-tumor tissues (median percentage of methylated reference, 29.16 vs. 42.82%, respectively; P=4×10 −8 ). Furthermore, results from receiver operating characteristic curve analysis identified a significant area under the curve of 0.706, with a sensitivity and a specificity of 77.8 and 58.1%, respectively, between cancer tissues and paired adjacent non-tumor tissues. Furthermore, the methylation of IL10 CGI was significantly associated with patients' age at diagnosis (r=−0.201; P=0.03). Subgroup analyses demonstrated that the association between IL10 CGI hypomethylation and the risk of GC was specific for patients with low differentiation (P=1×10 −7 ) and Borrmann types III+IV (P=1×10 −7 ). In addition, IL10 CGI hypomethylation was significantly associated with the risk of GC for patients without smoking history (P=3×10 −7 ) or a family history of cancer (P=2×10 −7 ). The results from Kaplan-Meier survival analysis demonstrated that IL10 CGI hypomethylation was associated with a significantly shorter overall survival of patients with GC (P=0.041). Similar results were identified for patients with GC who did not have smoking history (P=0.037) or a family history of cancer (P=0.049). The results from this study demonstrated that IL10 CGI hypomethylation may be considered as a potential biomarker for the diagnosis and prognosis of patients with GC in the Chinese population.
Protein tyrosine phosphatase non-receptor type 11 (PTPN11) encodes the tyrosine phosphatase SHP-2 that is overexpressed in gastric cancer (GC). In the present study, the association of PTPN11 methylation levels with the incidence of GC and its correlation with SHP-2 overexpression were investigated. The methylation levels of PTPN11 in tumor and adjacent normal tissues of 112 GC patients were assessed by quantitative methylation specific PCR (qMSP). The Cancer Genome Atlas (TCGA) public database was used to analyze the association between PTPN11 methylation and PTPN11 expression. Survival analyses were conducted in order to evaluate the prognostic value of PTPN11 methylation for GC. The results of the qMSP analysis indicated that the methylation levels of PTPN11 in GC tumor tissues were significantly decreased compared with those noted in the normal adjacent tissues (mean with standard deviation: 40.91±26.33 vs. 51.99±37.37, P=0.007). An inverse correlation between PTPN11 methylation levels and PTPN11 mRNA expression levels (P=4x10 -6 , r=-0.237) was noted. Subgroup analyses indicated that the association of PTPN11 hypomethylation with the incidence of GC was specific to male subjects (P= 0.015), heavy drinking patients (P=0.019), patients with poor tumor differentiation (P=0.010) and patients with tumor node and metastasis (TNM) stage III+IV (P=0.008). Kaplan-Meier analyses and log-rank test suggested that PTPN11 hypomethylation was not associated with GC patient overall survival (P=0.605) and recurrence (P=0.485), although it could predict the recurrence of GC patients up to and including 60 years (≤60, P=0.049). The results indicated that PTPN11 levels were hypomethylated in GC patients. TCGA data analysis suggested that PTPN11 hypomethylation could cause an upregulation in the transcription levels of PTPN11. Although, this may explain the pattern of SHP-2 overexpression in GC, additional studies are required to verify this hypothesis. The association of PTPN11 hypomethylation with GC incidence may be specific to male patients, heavy drinking patients, patients with poor tumor differentiation and patients with TNM stage of III+IV. PTPN11 hypomethylation can be considered a biomarker for the recurrence of GC patients with an age of 60 years or lower.
Background: Vascular endothelium and smooth muscle work together to keep the balance of vasomotor tone and jointly maintain vascular homeostasis. Ca 2+ -permeable ion channel TRPV4 (transient receptor potential vanilloid family member 4) in endothelial cells regulates endothelium-dependent vasodilation and contraction in various states. However, how vascular smooth muscle cell TRPV4 (TRPV4 SMC ) contributes to vascular function and blood pressure regulation in physiological and pathologically obese condition has not been fully studied. Methods: We generated smooth muscle TRPV4-deficient mice and developed diet-induced obese mice model and analyzed the role of TRPV4 SMC in intracellular Ca 2+ ([Ca 2+ ] i ) regulation and vasoconstriction. Vasomotor changes of mouse mesenteric artery were measured by wire, and pressure myography. [Ca 2+ ] i were measured by fluo-4 staining. Blood pressure was recorded by telemetric device. Results: Vascular TRPV4 SMC played different roles in regulating vasomotor tone than endothelial TRPV4 due to their different features of [Ca 2+ ] i regulation. Loss of TRPV4 SMC attenuated U46619- and phenylephrine-induced contraction, suggesting its involvement in regulating vascular contractility. Mesenteric arteries from obese mice showed SMC hyperplasia, suggesting an increased level of TRPV4 SMC . Loss of TRPV4 SMC did not influence the development of obesity but protected mice from obesity-induced vasoconstriction and hypertension. In arteries deficient in SMC TRPV4, SMCs F-actin polymerization and RhoA dephosphorylation were attenuated under contractile stimuli. Moreover, SMC-dependent vasoconstriction was inhibited in human resistance arteries with TRPV4 inhibitor application. Conclusions: Our data identify TRPV4 SMC as a regulator of vascular contraction in both physiological states and pathologically obese mice. TRPV4 SMC contributes to the ontogeny of vasoconstriction and hypertension induced by TRPV4 SMC over-expression in obese mice mesenteric artery.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.