AIM To examine the relationship between serum autotaxin(ATX) concentrations and clinicopathological findings in non-alcoholic fatty liver disease(NAFLD) patients.METHODS One hundred eighty-six NAFLD patients who had u...AIM To examine the relationship between serum autotaxin(ATX) concentrations and clinicopathological findings in non-alcoholic fatty liver disease(NAFLD) patients.METHODS One hundred eighty-six NAFLD patients who had undergone liver biopsy between 2008 and 2017 were retrospectively enrolled.Serum samples were collected at the time of biopsy and ATX was measured by enzyme immunoassays.Sera obtained from 160 healthy,nonobese individuals were used as controls.Histological findings were graded according to an NAFLD scoring system and correlations with serum ATX were calculated by Spearman's test.Diagnostic accuracy was evaluated using the area under the receiver operating characteristic curve(AUC).Cut-off values were identified by the Youden index,and the nearest clinically applicable value to the cutoff was considered the optimal threshold for clinical convenience.RESULTS Serum ATX levels were significantly higher in NAFLD patients than in controls(0.86 mg/L vs 0.76 mg/L,P < 0.001) and correlated significantly with ballooning score and fibrosis stage(r = 0.36,P < 0.001 and r = 0.45,P < 0.001,respectively).Such tendencies were stronger in female patients.There were no remarkable relationships between ATX and serum alanine aminotransferase,lipid profiles,or steatosis scores.The AUC values of ATX for predicting the presence of fibrosis(≥ F1),significant fibrosis(≥ F2),severe fibrosis(≥ F3),and cirrhosis(F4),were all more than 0.70 in respective analyses.CONCLUSION Serum ATX levels may at least partially reflect histological severity in NAFLD.展开更多
BACKGROUND Autotaxin(ATX)has been reported as a direct biomarker for estimating the evaluation of liver fibrosis.But available data on ATX as a useful biomarker for the complications of liver cirrhosis(LC)are scant.AI...BACKGROUND Autotaxin(ATX)has been reported as a direct biomarker for estimating the evaluation of liver fibrosis.But available data on ATX as a useful biomarker for the complications of liver cirrhosis(LC)are scant.AIM To assess the clinical usefulness of ATX for assessing the complications of LC.METHODS This multicenter,retrospective study was conducted at six locations in Japan.We include patients with LC,n=400.The ATX level was evaluated separately in men and women because of its high level in female patients.To assess the clinical usefulness of ATX for the complications of LC,the area under the curve(AUC)of ATX assessing for the severe complications was analyzed in comparison with the model for end-stage liver disease score,albumin-bilirubin(ALBI)score,fibrosis-4 index,and aspartate aminotransferase-to-platelet ratio index.RESULTS The mean age was 68.4±11.4 years,240 patients(60.0%)were male.A total of 213(53.3%)and 187(46.8%)patients were compensated and decompensated,respectively.The numbers of patients with varix rupture,hepatic ascites,and hepatic encephalopathy were 35(8.8%),131(32.8%),and 103(25.8%),respectively.The AUCs of ATX in men for hepatic encephalopathy,hepatic ascites,and varix ruptures were 0.853,0.816,and 0.706,respectively.The AUCs of ATX in women for hepatic encephalopathy,hepatic ascites,and varix rupture were 0.759,0.717,and 0.697,respectively.The AUCs of ATX in men were higher than those in women,as were all the other biomarkers used to detect encephalopathy and varix ruptures.However,for detecting ascites,the AUC of ALBI in men was more effective than using ATX.CONCLUSION ATX in men was more effective than any other biomarkers for detecting hepatic encephalopathy and varix ruptures.展开更多
The KAI1/CD82 gene inhibits the metastasis of most tumors and is remarkably correlated with tumor invasion and prognosis.Cell metabolism dysregulation is an important cause of tumor occurrence,development,and metastas...The KAI1/CD82 gene inhibits the metastasis of most tumors and is remarkably correlated with tumor invasion and prognosis.Cell metabolism dysregulation is an important cause of tumor occurrence,development,and metastasis.As one of the important characteristics of tumors,cell metabolism dysregulation is attracting increasing research attention.Phospholipids are an indispensable substance in the metabolism in various tumor cells.Phospholipid metabolites have become important cell signaling molecules.The pathological role of lysophosphatidic acid(LPA)in tumors was identified in the early 1990s.Currently,LPA inhibitors have entered clinical trials but are not yet used in clinical treatment.Autotaxin(ATX)has lysophospholipase D(lysoPLD)activity and can regulate LPA levels in vivo.The LPA receptor family and ATX/lysoPLD are abnormally expressed in various gastrointestinal tumors.According to our recent pre-experimental results,KAI1/CD82 might inhibit the migration and metastasis of cancer cells by regulating the ATX-LPA axis.However,no relevant research has been reported.Clarifying the mechanism of ATX-LPA in the inhibition of cancer metastasis by KAI1/CD82 will provide an important theoretical basis for targeted cancer therapy.In this paper,the molecular compositions of the KAI1/CD82 gene and the ATX-LPA axis,their physiological functions in tumors,and their roles in gastrointestinal cancers and target therapy are reviewed.展开更多
Autotaxin(ATX or ENPP2) is a secreted glycoprotein widely present in biological fluids. ATX primarily functions as a plasma lysophospholipase D and is largely responsible for the bulk of lysophosphatidic acid(LPA) pro...Autotaxin(ATX or ENPP2) is a secreted glycoprotein widely present in biological fluids. ATX primarily functions as a plasma lysophospholipase D and is largely responsible for the bulk of lysophosphatidic acid(LPA) production in the plasma and at inflamed and/or malignant sites. LPA is a phospholipid mediator produced in various conditions both in cells and in biological fluids, and it evokes growth-factor-like responses, including cell growth, survival, differentiation and motility, in almost all cell types. The large variety of LPA effector functions is attributed to at least six G-protein coupled LPA receptors(LPARs) with overlapping specificities and widespread distribution. Increased ATX/LPA/LPAR levels have been detected in a large variety of cancers and transformed cell lines, as well as in non-malignant inflamed tissues, suggesting a possible involvement of ATX in chronic inflammatory disorders and cancer. In this review, we focus exclusively on the role of the ATX/LPA axis in pulmonary pathophysiology, analysing the effects of ATX/LPA on pulmonary cells and leukocytes in vitro and in the context of pulmonary pathophysi-ological situations in vivo and in human diseases.展开更多
文摘AIM To examine the relationship between serum autotaxin(ATX) concentrations and clinicopathological findings in non-alcoholic fatty liver disease(NAFLD) patients.METHODS One hundred eighty-six NAFLD patients who had undergone liver biopsy between 2008 and 2017 were retrospectively enrolled.Serum samples were collected at the time of biopsy and ATX was measured by enzyme immunoassays.Sera obtained from 160 healthy,nonobese individuals were used as controls.Histological findings were graded according to an NAFLD scoring system and correlations with serum ATX were calculated by Spearman's test.Diagnostic accuracy was evaluated using the area under the receiver operating characteristic curve(AUC).Cut-off values were identified by the Youden index,and the nearest clinically applicable value to the cutoff was considered the optimal threshold for clinical convenience.RESULTS Serum ATX levels were significantly higher in NAFLD patients than in controls(0.86 mg/L vs 0.76 mg/L,P < 0.001) and correlated significantly with ballooning score and fibrosis stage(r = 0.36,P < 0.001 and r = 0.45,P < 0.001,respectively).Such tendencies were stronger in female patients.There were no remarkable relationships between ATX and serum alanine aminotransferase,lipid profiles,or steatosis scores.The AUC values of ATX for predicting the presence of fibrosis(≥ F1),significant fibrosis(≥ F2),severe fibrosis(≥ F3),and cirrhosis(F4),were all more than 0.70 in respective analyses.CONCLUSION Serum ATX levels may at least partially reflect histological severity in NAFLD.
文摘BACKGROUND Autotaxin(ATX)has been reported as a direct biomarker for estimating the evaluation of liver fibrosis.But available data on ATX as a useful biomarker for the complications of liver cirrhosis(LC)are scant.AIM To assess the clinical usefulness of ATX for assessing the complications of LC.METHODS This multicenter,retrospective study was conducted at six locations in Japan.We include patients with LC,n=400.The ATX level was evaluated separately in men and women because of its high level in female patients.To assess the clinical usefulness of ATX for the complications of LC,the area under the curve(AUC)of ATX assessing for the severe complications was analyzed in comparison with the model for end-stage liver disease score,albumin-bilirubin(ALBI)score,fibrosis-4 index,and aspartate aminotransferase-to-platelet ratio index.RESULTS The mean age was 68.4±11.4 years,240 patients(60.0%)were male.A total of 213(53.3%)and 187(46.8%)patients were compensated and decompensated,respectively.The numbers of patients with varix rupture,hepatic ascites,and hepatic encephalopathy were 35(8.8%),131(32.8%),and 103(25.8%),respectively.The AUCs of ATX in men for hepatic encephalopathy,hepatic ascites,and varix ruptures were 0.853,0.816,and 0.706,respectively.The AUCs of ATX in women for hepatic encephalopathy,hepatic ascites,and varix rupture were 0.759,0.717,and 0.697,respectively.The AUCs of ATX in men were higher than those in women,as were all the other biomarkers used to detect encephalopathy and varix ruptures.However,for detecting ascites,the AUC of ALBI in men was more effective than using ATX.CONCLUSION ATX in men was more effective than any other biomarkers for detecting hepatic encephalopathy and varix ruptures.
基金Supported by the National Natural Science Foundation of China,No.81672465the Science and Technology Program of Liaoning Province,No.2019JH8/10300080。
文摘The KAI1/CD82 gene inhibits the metastasis of most tumors and is remarkably correlated with tumor invasion and prognosis.Cell metabolism dysregulation is an important cause of tumor occurrence,development,and metastasis.As one of the important characteristics of tumors,cell metabolism dysregulation is attracting increasing research attention.Phospholipids are an indispensable substance in the metabolism in various tumor cells.Phospholipid metabolites have become important cell signaling molecules.The pathological role of lysophosphatidic acid(LPA)in tumors was identified in the early 1990s.Currently,LPA inhibitors have entered clinical trials but are not yet used in clinical treatment.Autotaxin(ATX)has lysophospholipase D(lysoPLD)activity and can regulate LPA levels in vivo.The LPA receptor family and ATX/lysoPLD are abnormally expressed in various gastrointestinal tumors.According to our recent pre-experimental results,KAI1/CD82 might inhibit the migration and metastasis of cancer cells by regulating the ATX-LPA axis.However,no relevant research has been reported.Clarifying the mechanism of ATX-LPA in the inhibition of cancer metastasis by KAI1/CD82 will provide an important theoretical basis for targeted cancer therapy.In this paper,the molecular compositions of the KAI1/CD82 gene and the ATX-LPA axis,their physiological functions in tumors,and their roles in gastrointestinal cancers and target therapy are reviewed.
基金Supported by National Grants from the Hellenic Ministry of Education,Lifelong Learning and Religious Affairs,No.09SYN-12-679/680
文摘Autotaxin(ATX or ENPP2) is a secreted glycoprotein widely present in biological fluids. ATX primarily functions as a plasma lysophospholipase D and is largely responsible for the bulk of lysophosphatidic acid(LPA) production in the plasma and at inflamed and/or malignant sites. LPA is a phospholipid mediator produced in various conditions both in cells and in biological fluids, and it evokes growth-factor-like responses, including cell growth, survival, differentiation and motility, in almost all cell types. The large variety of LPA effector functions is attributed to at least six G-protein coupled LPA receptors(LPARs) with overlapping specificities and widespread distribution. Increased ATX/LPA/LPAR levels have been detected in a large variety of cancers and transformed cell lines, as well as in non-malignant inflamed tissues, suggesting a possible involvement of ATX in chronic inflammatory disorders and cancer. In this review, we focus exclusively on the role of the ATX/LPA axis in pulmonary pathophysiology, analysing the effects of ATX/LPA on pulmonary cells and leukocytes in vitro and in the context of pulmonary pathophysi-ological situations in vivo and in human diseases.
