Background Studies have shown that kallikrein-related peptidase 7 (KLK7) is abnormally expressed in a various of tumours and plays a crucial role in tumour progression. The expression level and clinical significance of KLK7 in pancreatic cancer are still unclear. In this research, by detecting the expression of KLK7 in pancreatic cancer tissues and analyzing its relationship between clinicopathological characteristics and prognosis of patients with resectable pancreatic ductal adenocarcinoma (PDAC) as well as explore its clinical value in pancreatic cancer.MethodsWe compared the expression of KLK7 in public databases (TCGA and GTEx) between tumour tissues and normal pancreatic tissues. We used immunohistochemistry to detect the expression of KLK7 in 243 cases of PDAC tissues. For cancer patient data, the Kaplan-Meier survival curve and Cox risk model were using to analyzed the correlation between the KLK7 expression and the prognosis of pancreatic cancer patients. ResultsIn the TCGA and GTEx data sets, the expression of KLK7 in normal pancreatic tissue was obviously lower than in pancreatic cancer tissue (P<0.05). In the TCGA database data sets, the survival time of KLK7 high expression group was obviously lower than the low expression group (P<0.05). In the TCGA data set, we found that the expression of KLK7 can be using as an independent prognostic factor in pancreatic cancer patients (HR=1.32, 95% CI=1.118~1.559, P=0.001). Among 243 patients with clinical pancreatic cancer, the positive expression rate of KLK7 in pancreatic tumour tissue was obviously higher than in adjacent pancreatic tissue (P<0.001). The time to live of PDAC patients with high KLK7 expression is obviously lower than patients with common KLK7 expression (P<0.05). KLK7 expression, low tumour differentiation, nodal metastasis and vessel invasion were independently associated with poor overall survival (P<0.05). ConclusionsThe expression of KLK7 in patients with pancreatic ductal adenocarcinoma increased obviously, and it is directly related to the poor prognosis of patients after radical resection of pancreatic cancer. The expression of KLK7 may used as a predictor of long-term prognosis after radical resection of pancreatic cancer.
Brown adipocytes mainly utilize glucose and fatty acids to produce energy, which play key roles in thermogenesis. Furthermore, brown adipocytes also utilize other substrates, such as amino acids, for energy expenditure in various conditions. Here, we report the new physiological roles of proton-coupled amino acid transporters, SLC36A2 and SLC36A3, on global energy metabolism. The relative mRNA expression levels of both Slc36a2 and Slc36a3 were all highest in brown adipose tissue. We then generated global Slc36a2 and Slc36a3 knockout mice to investigate their functions in metabolism. Neither loss of Slc36a2 nor Slc36a3 affected the body weight and body composition of the mice. Slc36a2 knockout mice exhibited increased oxygen consumption during the daytime. After cold treatment, inhibition of Slc36a2 significantly decreased the mass of brown adipose tissue compared to wildtype mice, while it lowered the expression level of Cpt1a. Moreover, the serum lipid levels and liver mass were also decreased in Slc36a2 knockout mice after cold treatment. On the contrary, Slc36a3 knockout impaired glucose tolerance and up-regulated serum LDL-cholesterol concentration. Thus, SLC36A2 and SLC36A3 play central and different roles in the energy metabolism of the mice.
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