BACKGROUND The distal-less homeobox(DLX)gene family plays an important role in the development of several tumors.However,the expression pattern,prognostic and diagnostic value,possible regulatory mechanisms,and the re...BACKGROUND The distal-less homeobox(DLX)gene family plays an important role in the development of several tumors.However,the expression pattern,prognostic and diagnostic value,possible regulatory mechanisms,and the relationship between DLX family genes and immune infiltration in colon cancer have not been systematically reported.AIM We aimed to comprehensively analyze the biological role of the DLX gene family in the pathogenesis of colon cancer.METHODS Colon cancer tissue and normal colon tissue samples were collected from the Cancer Genome Atlas and Gene Expression Omnibus databases.Wilcoxon rank sum test and t-test were used to assess DLX gene family expression between colon cancer tissue and unpaired normal colon tissue.cBioPortal was used to analyze DLX gene family variants.R software was used to analyze DLX gene expression in colon cancer and the relationship between DLX gene family expression and clinical features and correlation heat map.The survival package and Cox regression module were used to assess the prognostic value of the DLX gene family.The pROC package was used to analyze the diagnostic value of the DLX gene family.R software was used to analyze the possible regulatory mechanisms of DLX gene family members and related genes.The GSVA package was used to analyze the relationship between the DLX gene family and immune infiltration.The ggplot2,the survminer package,and the clusterProfiler package were used for visualization.RESULTS DLX1/2/3/4/5 were significantly aberrantly expressed in colon cancer patients.The expression of DLX genes were associated with M stage,pathologic stage,primary therapy outcome,residual tumor,lymphatic invasion,T stage,N stage,age,perineural invasion,and history of colon polyps.DLX5 was independently correlated with the prognosis of colon cancer in multivariate analysis.DLX1/2/3/4/5/6 were involved in the development and progression of colon cancer by participating in immune infiltration and associated pathways,including the Hippo signaling pathway,the Wnt signaling pathway,several signaling pathways regulating the pluripotency of stem cells,and Staphylococcus aureus infection.CONCLUSION The results of this study suggest a possible role for the DLX gene family as potential diagnostic or prognostic biomarkers and therapeutic targets in colon cancer.展开更多
目的基于骨组织Dlx5启动子甲基化水平,探索补肾中药复方对大鼠去卵巢骨质疏松症的疗效机制。方法去卵巢建立绝经后骨质疏松症(postmenopausal osteoporosis,PMOP)大鼠模型,分为正常组、模型组、补肾中药复方组、仙灵骨葆阳性对照组。灌...目的基于骨组织Dlx5启动子甲基化水平,探索补肾中药复方对大鼠去卵巢骨质疏松症的疗效机制。方法去卵巢建立绝经后骨质疏松症(postmenopausal osteoporosis,PMOP)大鼠模型,分为正常组、模型组、补肾中药复方组、仙灵骨葆阳性对照组。灌胃14周后,X线吸收测量法检测骨密度,质谱法检测Dlx5启动子甲基化水平。结果与正常组比较,模型组第1~6腰椎骨密度明显降低(P<0.01),骨组织Dlx5启动子-470 bp^-4 bp CpG2.3甲基化水平明显升高(P<0.01)。②与模型组比较,补肾中药复方组、仙灵骨葆阳性对照组第1~6腰椎骨密度明显升高(P<0.05),骨组织Dlx5启动子-470 bp^-4 bp CpG1甲基化水平明显降低(P<0.05)。结论补肾中药复方通过降低骨组织Dlx5启动子甲基化水平的表观遗传学机制,有效防治PMOP。展开更多
AIM:To characterize the regeneration-associated stem cell-related phenotype of hepatocyte-derived growth factor receptor(HGFR)-expressing cells in active ulcerative colitis(UC).METHODS:On the whole 38 peripheral blood...AIM:To characterize the regeneration-associated stem cell-related phenotype of hepatocyte-derived growth factor receptor(HGFR)-expressing cells in active ulcerative colitis(UC).METHODS:On the whole 38 peripheral blood samples and 38 colonic biopsy samples from 18 patients with histologically proven active UC and 20 healthy control subjects were collected.After preparing tissue microarrays and blood smears HGFR,caudal type homeobox 2(CDX2),prominin-1(CD133) and Musashi-1conventional and double fluorescent immunolabelings were performed.Immunostained samples were digitalized using high-resolution Mirax Desk instrument,and analyzed with the Mirax TMA Module software.For semiquantitative counting of immunopositive lamina propria(LP) cells 5 fields of view were counted at magnification x 200 in each sample core,then mean ± SD were determined.In case of peripheral blood smears,30 fields of view with 100 μm diameter were evaluated in every sample and the number of immunopositive cells(mean ± SD) was determined.Using 337 nm UVA Laser MicroDissection system at least 5000 subepithelial cells from the lamina propria were collected.Gene expression analysis of HGFR,CDX2,CD133,leucine-rich repeat-containing G-protein coupled receptor 5(Lgr5),Musashi-1 and cytokeratin20(CK20) were performed in both laser-microdisscted samples and blood samples by using real time reverse transcription polymerase chain reaction(RT-PCR).RESULTS:By performing conventional and double fluorescent immunolabelings confirmed by RT-PCR,higher number of HGFR(blood:6.7 ± 1.22 vs 38.5 ±3.18;LP:2.25 ± 0.85 vs 9.22 ± 0.65;P < 0.05),CDX2(blood:0 vs 0.94 ± 0.64;LP:0.75 ± 0.55 vs 2.11± 0.75;P < 0.05),CD133(blood:1.1 ± 0.72 vs 8.3± 1.08;LP:11.1 ± 0.85 vs 26.28 ± 1.71;P < 0.05)and Musashi-1(blood and LP:0 vs scattered) positive cells were detected in blood and lamina propria of UC samples as compared to controls.HGFR/CDX2(blood:0 vs 1± 0.59;LP:0.8 ± 0.69 vs 2.06 ± 0.72,P < 0.05)and Musashi-1/CDX2(blood and LP:0 vs scattered) coexpressions were found in blood and lamina propria of UC samples.HGFR/CD133 and CD133/CDX2 coexpressions appeared only in UC lamina propria samples.CDX2,Lgr5 and Musashi-1 expressions in UC blood samples were not accompanied by CK20 mRNA expression.CONCLUSION:In active UC,a portion of circulating HGFR-expressing cells are committed to the epithelial lineage,and may participate in mucosal regeneration by undergoing mesenchymal-to-epithelial transition.展开更多
文摘BACKGROUND The distal-less homeobox(DLX)gene family plays an important role in the development of several tumors.However,the expression pattern,prognostic and diagnostic value,possible regulatory mechanisms,and the relationship between DLX family genes and immune infiltration in colon cancer have not been systematically reported.AIM We aimed to comprehensively analyze the biological role of the DLX gene family in the pathogenesis of colon cancer.METHODS Colon cancer tissue and normal colon tissue samples were collected from the Cancer Genome Atlas and Gene Expression Omnibus databases.Wilcoxon rank sum test and t-test were used to assess DLX gene family expression between colon cancer tissue and unpaired normal colon tissue.cBioPortal was used to analyze DLX gene family variants.R software was used to analyze DLX gene expression in colon cancer and the relationship between DLX gene family expression and clinical features and correlation heat map.The survival package and Cox regression module were used to assess the prognostic value of the DLX gene family.The pROC package was used to analyze the diagnostic value of the DLX gene family.R software was used to analyze the possible regulatory mechanisms of DLX gene family members and related genes.The GSVA package was used to analyze the relationship between the DLX gene family and immune infiltration.The ggplot2,the survminer package,and the clusterProfiler package were used for visualization.RESULTS DLX1/2/3/4/5 were significantly aberrantly expressed in colon cancer patients.The expression of DLX genes were associated with M stage,pathologic stage,primary therapy outcome,residual tumor,lymphatic invasion,T stage,N stage,age,perineural invasion,and history of colon polyps.DLX5 was independently correlated with the prognosis of colon cancer in multivariate analysis.DLX1/2/3/4/5/6 were involved in the development and progression of colon cancer by participating in immune infiltration and associated pathways,including the Hippo signaling pathway,the Wnt signaling pathway,several signaling pathways regulating the pluripotency of stem cells,and Staphylococcus aureus infection.CONCLUSION The results of this study suggest a possible role for the DLX gene family as potential diagnostic or prognostic biomarkers and therapeutic targets in colon cancer.
文摘目的基于骨组织Dlx5启动子甲基化水平,探索补肾中药复方对大鼠去卵巢骨质疏松症的疗效机制。方法去卵巢建立绝经后骨质疏松症(postmenopausal osteoporosis,PMOP)大鼠模型,分为正常组、模型组、补肾中药复方组、仙灵骨葆阳性对照组。灌胃14周后,X线吸收测量法检测骨密度,质谱法检测Dlx5启动子甲基化水平。结果与正常组比较,模型组第1~6腰椎骨密度明显降低(P<0.01),骨组织Dlx5启动子-470 bp^-4 bp CpG2.3甲基化水平明显升高(P<0.01)。②与模型组比较,补肾中药复方组、仙灵骨葆阳性对照组第1~6腰椎骨密度明显升高(P<0.05),骨组织Dlx5启动子-470 bp^-4 bp CpG1甲基化水平明显降低(P<0.05)。结论补肾中药复方通过降低骨组织Dlx5启动子甲基化水平的表观遗传学机制,有效防治PMOP。
基金Cell Analysis Laboratory, 2nd Department of Internal Medicine, and the 1st Department of Pathology and Experimental Oncology, Semmelweis University for their technical support
文摘AIM:To characterize the regeneration-associated stem cell-related phenotype of hepatocyte-derived growth factor receptor(HGFR)-expressing cells in active ulcerative colitis(UC).METHODS:On the whole 38 peripheral blood samples and 38 colonic biopsy samples from 18 patients with histologically proven active UC and 20 healthy control subjects were collected.After preparing tissue microarrays and blood smears HGFR,caudal type homeobox 2(CDX2),prominin-1(CD133) and Musashi-1conventional and double fluorescent immunolabelings were performed.Immunostained samples were digitalized using high-resolution Mirax Desk instrument,and analyzed with the Mirax TMA Module software.For semiquantitative counting of immunopositive lamina propria(LP) cells 5 fields of view were counted at magnification x 200 in each sample core,then mean ± SD were determined.In case of peripheral blood smears,30 fields of view with 100 μm diameter were evaluated in every sample and the number of immunopositive cells(mean ± SD) was determined.Using 337 nm UVA Laser MicroDissection system at least 5000 subepithelial cells from the lamina propria were collected.Gene expression analysis of HGFR,CDX2,CD133,leucine-rich repeat-containing G-protein coupled receptor 5(Lgr5),Musashi-1 and cytokeratin20(CK20) were performed in both laser-microdisscted samples and blood samples by using real time reverse transcription polymerase chain reaction(RT-PCR).RESULTS:By performing conventional and double fluorescent immunolabelings confirmed by RT-PCR,higher number of HGFR(blood:6.7 ± 1.22 vs 38.5 ±3.18;LP:2.25 ± 0.85 vs 9.22 ± 0.65;P < 0.05),CDX2(blood:0 vs 0.94 ± 0.64;LP:0.75 ± 0.55 vs 2.11± 0.75;P < 0.05),CD133(blood:1.1 ± 0.72 vs 8.3± 1.08;LP:11.1 ± 0.85 vs 26.28 ± 1.71;P < 0.05)and Musashi-1(blood and LP:0 vs scattered) positive cells were detected in blood and lamina propria of UC samples as compared to controls.HGFR/CDX2(blood:0 vs 1± 0.59;LP:0.8 ± 0.69 vs 2.06 ± 0.72,P < 0.05)and Musashi-1/CDX2(blood and LP:0 vs scattered) coexpressions were found in blood and lamina propria of UC samples.HGFR/CD133 and CD133/CDX2 coexpressions appeared only in UC lamina propria samples.CDX2,Lgr5 and Musashi-1 expressions in UC blood samples were not accompanied by CK20 mRNA expression.CONCLUSION:In active UC,a portion of circulating HGFR-expressing cells are committed to the epithelial lineage,and may participate in mucosal regeneration by undergoing mesenchymal-to-epithelial transition.
