Chronic enteropathy associated with the SLCO2A1 gene(CEAS)is a complex gastroenterological condition characterized by multiple ulcers in the small intestine with chronic bleeding and protein loss.This review explores ...Chronic enteropathy associated with the SLCO2A1 gene(CEAS)is a complex gastroenterological condition characterized by multiple ulcers in the small intestine with chronic bleeding and protein loss.This review explores the potential mechanisms underlying the pathogenesis of CEAS,focusing on the role of SLCO2A1-encoded prostaglandin transporter OATP2A1 and its impact on prostaglandin E2(PGE2)levels.Studies have suggested that elevated PGE2 levels contribute to mucosal damage,inflammation,and disruption of the intestinal barrier.The effects of PGE2 on macrophage activation and Maxi-Cl channel functionality,as well as its interaction with nonsteroidal anti-inflammatory drugs play crucial roles in the progression of CEAS.Understanding the balance between its protective and pro-inflammatory effects and the complex interactions within the gastrointestinal tract can shed light on potential therapeutic targets for CEAS and guide the development of novel,targeted therapies.展开更多
目的探讨肿瘤蛋白p53诱导的核蛋白2(tumor protein p53 inducible nuclear protein 2,TP53INP2)和溶质载体有机阴离子转运蛋白家族成员2A1(solute carrier organic anion transporter family member 2A1,SLCO2A1)在分化型甲状腺癌(diffe...目的探讨肿瘤蛋白p53诱导的核蛋白2(tumor protein p53 inducible nuclear protein 2,TP53INP2)和溶质载体有机阴离子转运蛋白家族成员2A1(solute carrier organic anion transporter family member 2A1,SLCO2A1)在分化型甲状腺癌(differentiated thyroid carcinoma,DTC)中的表达及其与临床病理特征和预后的关系。方法选取2024年3月至5月于南京医科大学第三附属医院行甲状腺癌根治术的DTC患者80例,比较TP53INP2和SLCO2A1在DTC患者的癌组织、癌旁组织及淋巴结转移组织中的表达,分析其与DTC患者临床病理特征之间的关系。从癌症基因组图谱(The Cancer GenomeAtlas,TCGA)数据库下载正常人甲状腺和DTC组织的表达矩阵、临床病理参数及预后资料,使用R软件进行基因集变异分析(gene set variation analysis,GSVA),分析GSVA评分与DTC患者临床病理特征及预后之间的关系。采用Kaplan-Meier法分析基因集GSVA评分与DTC患者无进展生存(progress free survive,PFS)之间的关系。采用Cox单因素及多因素分析探讨影响DTC患者预后的因素。结果DTC患者癌组织及淋巴结转移组织中的TP53INP2和SLCO2A1表达显著降低(P<0.05)。GSVA评分与肿瘤侵袭、淋巴结转移、远处转移和病理类型显著相关(P<0.05)。GSVA评分低的DTC患者的PFS率显著低于GSVA评分高者(P=0.002)。Cox多因素分析结果显示肿瘤侵袭及GSVA评分低均是导致DTC患者预后不良的独立影响因素(P<0.05)。结论TP53INP2和SLCO2A1在DTC组织中表达降低,其表达降低与肿瘤侵袭、淋巴结转移、远处转移及不良预后有关,或可成为DTC患者预后判断的潜在靶点。展开更多
BACKGROUND Eosinophilic gastrointestinal disease(EGID)is a disorder characterized by infiltration of eosinophils causing mucosal damage and dysfunction of the gastrointestinal tract.The endoscopic findings of eosinoph...BACKGROUND Eosinophilic gastrointestinal disease(EGID)is a disorder characterized by infiltration of eosinophils causing mucosal damage and dysfunction of the gastrointestinal tract.The endoscopic findings of eosinophilic enteritis(EoN),an EGID variant,are nonspecific and occasionally difficult to diagnose.In contrast,chronic enteropathy associated with SLCO2A1(CEAS)is a chronic persistent small intestinal disorder characterized by endoscopic findings such as multiple oblique and circular ulcers.CASE SUMMARY We report the case of a 10-year-old boy who had suffered abdominal pain and fatigue for the preceding 6 mo.He was referred to our institute for investigation of suspected gastrointestinal bleeding because of severe anemia with hypoproteinemia and positive fecal human hemoglobin.The upper and lower gastrointestinal endoscopic findings were normal;however,double-balloon small bowel endoscopy showed multiple oblique and circular ulcers with discrete margins and mild constriction of the intestinal lumen in the ileum.The findings were highly consistent with CEAS,but urine prostaglandin metabolites were within normal limits,and no previously reported mutations in the SLCO2A1 gene were identified.Histological evaluation demonstrated moderate to severe eosinophilic infiltration localized to the small intestine suggesting a diagnosis of EoN.Clinical remission was maintained with montelukast and a partial elemental diet,but emergent surgery for bowel obstruction due to small intestinal stenosis was performed two years after the initial treatment.CONCLUSION EoN should be considered in the differential diagnosis of CEAS-like small intestinal ulcerative lesions and normal urinary prostaglandin metabolite levels.展开更多
溶质载体有机阴离子转运蛋白家族成员2A1(solute carrier organic anion transporter family member 2A1,SLCO2A1)基因相关慢性肠病(chronic enteropathy associated with SLCO2A1 gene,CEAS)是一种因SLCO2A1基因突变所致的常染色体隐...溶质载体有机阴离子转运蛋白家族成员2A1(solute carrier organic anion transporter family member 2A1,SLCO2A1)基因相关慢性肠病(chronic enteropathy associated with SLCO2A1 gene,CEAS)是一种因SLCO2A1基因突变所致的常染色体隐性遗传病,特征在于持续性、顽固性、非特异性小肠溃疡导致血液和蛋白质慢性丢失。目前CEAS发病机制尚不明确,内镜检查可见特异性小肠溃疡及肠腔狭窄,病变部位以回肠为主。因发病罕见,且临床表现与克罗恩病、非甾体抗炎药相关性肠病等疾病相似,临床容易混淆。治疗上尚未建立有效的方法,可予补铁、输血及肠内或肠外营养对症治疗,病情严重时可行外科治疗,但均疗效短暂,通常在治疗结束后病情反复,生命预后尚不明确。展开更多
BACKGROUND We recently reported on a hereditary enteropathy associated with a gene encoding a prostaglandin transporter and referred to as chronic enteropathy associated with SLCO2 A1 gene(CEAS).Crohn's disease(CD...BACKGROUND We recently reported on a hereditary enteropathy associated with a gene encoding a prostaglandin transporter and referred to as chronic enteropathy associated with SLCO2 A1 gene(CEAS).Crohn's disease(CD)is a major differential diagnosis of CEAS,because these diseases share some clinical features.Therefore,there is a need to develop a convenient screening test to distinguish CEAS from CD.AIM To examine whether prostaglandin E major urinary metabolites(PGE-MUM)can serve as a biomarker to distinguish CEAS from CD.METHODS This was a transactional study of 20 patients with CEAS and 98 patients with CD.CEAS was diagnosed by the confirmation of homozygous or compound heterozygous mutation of SLCO2 A1.We measured the concentration of PGEMUM in spot urine by radioimmunoassay,and the concentration was compared between the two groups of patients.We also determined the optimal cut-off value of PGE-MUM to distinguish CEAS from CD by receiver operating characteristic(ROC)curve analysis.RESULTS Twenty Japanese patients with CEAS and 98 patients with CD were enrolled.PGE-MUM concentration in patients with CEAS was significantly higher than that in patients with CD(median 102.7 vs 27.9μg/g×Cre,P<0.0001).One log unit increase in PGE-MUM contributed to 7.3 increase in the likelihood for the diagnosis of CEAS[95%confidence interval(CI)3.2-16.7].A logistic regression analysis revealed that the association was significant even after adjusting confounding factors(adjusted odds ratio 29.6,95%CI 4.7-185.7).ROC curve analysis revealed the optimal PGE-MUM cut-off value for the distinction of CEAS from CD to be 48.9μg/g×Cre with 95.0%sensitivity and 79.6%specificity.CONCLUSION PGE-MUM measurement is a convenient,non-invasive and useful test for the distinction of CEAS from CD.展开更多
The widespread use of capsule endoscopy and balloonassisted endoscopy has provided easy access for detailed mucosal assessment of the small intestine. However, the diagnosis of rare small bowel diseases, such as crypt...The widespread use of capsule endoscopy and balloonassisted endoscopy has provided easy access for detailed mucosal assessment of the small intestine. However, the diagnosis of rare small bowel diseases, such as cryptogenic multifocal ulcerous stenosing enteritis(CMUSE), remains difficult because clinical and morphological features of these diseases are obscure even for gastroenterologists. In an issue of this journal in 2017, Hwang et al reviewed and summarized clinical and radiographic features of 20 patients with an established diagnosis of CMUSE. Recently, recessive mutations in the PLA2G4A and SLCO2A1 genes have been shown to cause small intestinal diseases. The small bowel ulcers in each disease mimic those in the other and furthermore those found in nonsteroidal anti-inflammatory drug-induced enteropathy. These recent and novel findings suggest that a clinical diagnosis exclusively based on the characteristics of small bowel lesions is possibly imprecise. Genetic analyses seem to be inevitable for the diagnosis of rare small bowel disorders such as CMUSE.展开更多
基金Supported by the National High-Level Hospital Clinical Research Fund,No.2022-PUMCH-A-020the Undergraduate Teaching Reform and Innovation Project,No.2022zlgc0108.
文摘Chronic enteropathy associated with the SLCO2A1 gene(CEAS)is a complex gastroenterological condition characterized by multiple ulcers in the small intestine with chronic bleeding and protein loss.This review explores the potential mechanisms underlying the pathogenesis of CEAS,focusing on the role of SLCO2A1-encoded prostaglandin transporter OATP2A1 and its impact on prostaglandin E2(PGE2)levels.Studies have suggested that elevated PGE2 levels contribute to mucosal damage,inflammation,and disruption of the intestinal barrier.The effects of PGE2 on macrophage activation and Maxi-Cl channel functionality,as well as its interaction with nonsteroidal anti-inflammatory drugs play crucial roles in the progression of CEAS.Understanding the balance between its protective and pro-inflammatory effects and the complex interactions within the gastrointestinal tract can shed light on potential therapeutic targets for CEAS and guide the development of novel,targeted therapies.
文摘目的探讨肿瘤蛋白p53诱导的核蛋白2(tumor protein p53 inducible nuclear protein 2,TP53INP2)和溶质载体有机阴离子转运蛋白家族成员2A1(solute carrier organic anion transporter family member 2A1,SLCO2A1)在分化型甲状腺癌(differentiated thyroid carcinoma,DTC)中的表达及其与临床病理特征和预后的关系。方法选取2024年3月至5月于南京医科大学第三附属医院行甲状腺癌根治术的DTC患者80例,比较TP53INP2和SLCO2A1在DTC患者的癌组织、癌旁组织及淋巴结转移组织中的表达,分析其与DTC患者临床病理特征之间的关系。从癌症基因组图谱(The Cancer GenomeAtlas,TCGA)数据库下载正常人甲状腺和DTC组织的表达矩阵、临床病理参数及预后资料,使用R软件进行基因集变异分析(gene set variation analysis,GSVA),分析GSVA评分与DTC患者临床病理特征及预后之间的关系。采用Kaplan-Meier法分析基因集GSVA评分与DTC患者无进展生存(progress free survive,PFS)之间的关系。采用Cox单因素及多因素分析探讨影响DTC患者预后的因素。结果DTC患者癌组织及淋巴结转移组织中的TP53INP2和SLCO2A1表达显著降低(P<0.05)。GSVA评分与肿瘤侵袭、淋巴结转移、远处转移和病理类型显著相关(P<0.05)。GSVA评分低的DTC患者的PFS率显著低于GSVA评分高者(P=0.002)。Cox多因素分析结果显示肿瘤侵袭及GSVA评分低均是导致DTC患者预后不良的独立影响因素(P<0.05)。结论TP53INP2和SLCO2A1在DTC组织中表达降低,其表达降低与肿瘤侵袭、淋巴结转移、远处转移及不良预后有关,或可成为DTC患者预后判断的潜在靶点。
基金Supported by a Japan Society for the Promotion of Science KAKENHI Grant-in-Aid for Young Scientists,No.20K16905.
文摘BACKGROUND Eosinophilic gastrointestinal disease(EGID)is a disorder characterized by infiltration of eosinophils causing mucosal damage and dysfunction of the gastrointestinal tract.The endoscopic findings of eosinophilic enteritis(EoN),an EGID variant,are nonspecific and occasionally difficult to diagnose.In contrast,chronic enteropathy associated with SLCO2A1(CEAS)is a chronic persistent small intestinal disorder characterized by endoscopic findings such as multiple oblique and circular ulcers.CASE SUMMARY We report the case of a 10-year-old boy who had suffered abdominal pain and fatigue for the preceding 6 mo.He was referred to our institute for investigation of suspected gastrointestinal bleeding because of severe anemia with hypoproteinemia and positive fecal human hemoglobin.The upper and lower gastrointestinal endoscopic findings were normal;however,double-balloon small bowel endoscopy showed multiple oblique and circular ulcers with discrete margins and mild constriction of the intestinal lumen in the ileum.The findings were highly consistent with CEAS,but urine prostaglandin metabolites were within normal limits,and no previously reported mutations in the SLCO2A1 gene were identified.Histological evaluation demonstrated moderate to severe eosinophilic infiltration localized to the small intestine suggesting a diagnosis of EoN.Clinical remission was maintained with montelukast and a partial elemental diet,but emergent surgery for bowel obstruction due to small intestinal stenosis was performed two years after the initial treatment.CONCLUSION EoN should be considered in the differential diagnosis of CEAS-like small intestinal ulcerative lesions and normal urinary prostaglandin metabolite levels.
文摘溶质载体有机阴离子转运蛋白家族成员2A1(solute carrier organic anion transporter family member 2A1,SLCO2A1)基因相关慢性肠病(chronic enteropathy associated with SLCO2A1 gene,CEAS)是一种因SLCO2A1基因突变所致的常染色体隐性遗传病,特征在于持续性、顽固性、非特异性小肠溃疡导致血液和蛋白质慢性丢失。目前CEAS发病机制尚不明确,内镜检查可见特异性小肠溃疡及肠腔狭窄,病变部位以回肠为主。因发病罕见,且临床表现与克罗恩病、非甾体抗炎药相关性肠病等疾病相似,临床容易混淆。治疗上尚未建立有效的方法,可予补铁、输血及肠内或肠外营养对症治疗,病情严重时可行外科治疗,但均疗效短暂,通常在治疗结束后病情反复,生命预后尚不明确。
基金Supported by the Practical Research Project for Rare/Intractable Diseases from the Japan Agency for Medical Research and Development(AMED),No.15ek0109053h0002 to Matsumoto Tby grants from the Japan Society for the Promotion of Science(JSPS)KAKENHI,No.25460953,to Umeno J,Esaki M,and Matsumoto T
文摘BACKGROUND We recently reported on a hereditary enteropathy associated with a gene encoding a prostaglandin transporter and referred to as chronic enteropathy associated with SLCO2 A1 gene(CEAS).Crohn's disease(CD)is a major differential diagnosis of CEAS,because these diseases share some clinical features.Therefore,there is a need to develop a convenient screening test to distinguish CEAS from CD.AIM To examine whether prostaglandin E major urinary metabolites(PGE-MUM)can serve as a biomarker to distinguish CEAS from CD.METHODS This was a transactional study of 20 patients with CEAS and 98 patients with CD.CEAS was diagnosed by the confirmation of homozygous or compound heterozygous mutation of SLCO2 A1.We measured the concentration of PGEMUM in spot urine by radioimmunoassay,and the concentration was compared between the two groups of patients.We also determined the optimal cut-off value of PGE-MUM to distinguish CEAS from CD by receiver operating characteristic(ROC)curve analysis.RESULTS Twenty Japanese patients with CEAS and 98 patients with CD were enrolled.PGE-MUM concentration in patients with CEAS was significantly higher than that in patients with CD(median 102.7 vs 27.9μg/g×Cre,P<0.0001).One log unit increase in PGE-MUM contributed to 7.3 increase in the likelihood for the diagnosis of CEAS[95%confidence interval(CI)3.2-16.7].A logistic regression analysis revealed that the association was significant even after adjusting confounding factors(adjusted odds ratio 29.6,95%CI 4.7-185.7).ROC curve analysis revealed the optimal PGE-MUM cut-off value for the distinction of CEAS from CD to be 48.9μg/g×Cre with 95.0%sensitivity and 79.6%specificity.CONCLUSION PGE-MUM measurement is a convenient,non-invasive and useful test for the distinction of CEAS from CD.
基金Supported by the Practical Research Project for Rare/Intractable Diseases from Japan Agency for Medical Research and Development(AMED),No.15ek0109053h0002the Japan Society for the Promotion of Science(JSPS)KAKENHI,No.25460953
文摘The widespread use of capsule endoscopy and balloonassisted endoscopy has provided easy access for detailed mucosal assessment of the small intestine. However, the diagnosis of rare small bowel diseases, such as cryptogenic multifocal ulcerous stenosing enteritis(CMUSE), remains difficult because clinical and morphological features of these diseases are obscure even for gastroenterologists. In an issue of this journal in 2017, Hwang et al reviewed and summarized clinical and radiographic features of 20 patients with an established diagnosis of CMUSE. Recently, recessive mutations in the PLA2G4A and SLCO2A1 genes have been shown to cause small intestinal diseases. The small bowel ulcers in each disease mimic those in the other and furthermore those found in nonsteroidal anti-inflammatory drug-induced enteropathy. These recent and novel findings suggest that a clinical diagnosis exclusively based on the characteristics of small bowel lesions is possibly imprecise. Genetic analyses seem to be inevitable for the diagnosis of rare small bowel disorders such as CMUSE.
