BACKGROUND Breast infiltrating ductal carcinoma(BIDC)represents the largest heterotypic tumor group,and an in-depth understanding of the pathogenesis of BIDC is key to improving its prognosis.AIM To analyze the expres...BACKGROUND Breast infiltrating ductal carcinoma(BIDC)represents the largest heterotypic tumor group,and an in-depth understanding of the pathogenesis of BIDC is key to improving its prognosis.AIM To analyze the expression profiles and clinical implications of forkhead box M1(FOXM1),cyclooxygenase-2(COX-2),and glucose-regulated protein 78(GRP78)in BIDC.METHODS A total of 65 BIDC patients and 70 healthy controls who presented to our hospital between August 2019 and May 2021 were selected for analysis.The peripheral blood FOXM1,COX-2,and GRP78 levels in both groups were measured and the association between their expression profiles in BIDC was examined.Additionally,we investigated the diagnostic value of FOXM1,COX-2,and GRP78 in patients with BIDC and their correlations with clinicopathological features.Furthermore,BIDC patients were followed for 1 year to identify factors influencing patient prognosis.RESULTS The levels of FOXM1,COX-2,and GRP78 were significantly higher in BIDC patients compared to healthy controls(P<0.05),and a positive correlation was observed among them(P<0.05).Receiver operating characteristic analysis demonstrated that FOXM1,COX-2,and GRP78 had excellent diagnostic value in predicting the occurrence of BIDC(P<0.05).Subsequently,we found significant differences in FOXM1,COX-2,and GRP78 levels among patients with different histological grades and metastasis statuses(with vs without)(P<0.05).Cox analysis revealed that FOXM1,COX-2,GRP78,increased histological grade,and the presence of tumor metastasis were independent risk factors for prognostic death in BIDC(P<0.001).CONCLUSION FOXM1,COX-2,and GRP78 exhibit abnormally high expression in BIDC,promoting malignant tumor development and closely correlating with prognosis.These findings hold significant research implications for the future diagnosis and treatment of BIDC.展开更多
AIM: To investigate the expression of forkhead box protein M1(Fox M1) in the process of epithelial mesenchymal transition in hepatocellular carcinoma(HCC) and its role in metastasis.METHODS: Fox M1 and E-cadherin expr...AIM: To investigate the expression of forkhead box protein M1(Fox M1) in the process of epithelial mesenchymal transition in hepatocellular carcinoma(HCC) and its role in metastasis.METHODS: Fox M1 and E-cadherin expression in HCC tissue microarray specimens was evaluated by immunohistochemical staining,and statistical methods were applied to analyze the correlation between FoxM 1 and epithelial-mesenchymal transition(EMT).KaplanMeier analysis of the correlation between the Fox M1 expression level and recurrence or overall survival of HCC patients was performed.The expression of FoxM 1,E-cadherin and snail homologue 1(SNAI1) in HCC cell lines was evaluated by real-time reverse transcriptionpolymerase chain reaction and Western blot.Hepatocyte growth factor(HGF) was used to induce EMT and stimulate cell migration in HCC cells.The expression of Fox M1 and SNAI1 was regulated by transfection with plasmids pc DNA3.1 and si RNAs in vitro.The occurrence of EMT was evaluated by Transwell assay,morphologic analysis and detection of the expression of EMT markers(E-cadherin and vimentin).Luciferase and chromatin immunoprecipitation assays were used to evaluate whether SNAI1 is a direct transcriptional target of FoxM 1.RESULTS: FoxM 1 expression was increased significantly in HCC compared with para-carcinoma(10.7 ± 0.9 vs 8.2 ± 0.7,P < 0.05) and normal hepatic(10.7 ± 0.9 vs 2.7 ± 0.4,P < 0.05) tissues.Overexpression of Fox M1 was correlated with HCC tumor size,tumor number,macrovascular invasion and higher TNM stage,but was negatively correlated with E-cadherin expression in microarray specimens and in cell lines.Fox M1 overexpression was correlated significantly with HCC metastasis and EMT.In vitro,we found that FoxM 1 plays a key role in HGF-induced EMT,and overexpression of Fox M1 could suppress E-cadherin expression and induce EMT changes,which were associated with increased HCC cell invasiveness.Next,we confirmed that FOXM1 directly binds to and activates the SNAI1 promoter,and we identified SNAI1 as a direct transcriptional target of FOXM1.Moreover,inhibiting the expression of SNAI1 significantly inhibited FoxM 1-mediated EMT.CONCLUSION: Fox M1 overexpression promotes EMT and metastasis of HCC,and SNAI1 plays a critical role in FoxM 1-mediated EMT.展开更多
文摘BACKGROUND Breast infiltrating ductal carcinoma(BIDC)represents the largest heterotypic tumor group,and an in-depth understanding of the pathogenesis of BIDC is key to improving its prognosis.AIM To analyze the expression profiles and clinical implications of forkhead box M1(FOXM1),cyclooxygenase-2(COX-2),and glucose-regulated protein 78(GRP78)in BIDC.METHODS A total of 65 BIDC patients and 70 healthy controls who presented to our hospital between August 2019 and May 2021 were selected for analysis.The peripheral blood FOXM1,COX-2,and GRP78 levels in both groups were measured and the association between their expression profiles in BIDC was examined.Additionally,we investigated the diagnostic value of FOXM1,COX-2,and GRP78 in patients with BIDC and their correlations with clinicopathological features.Furthermore,BIDC patients were followed for 1 year to identify factors influencing patient prognosis.RESULTS The levels of FOXM1,COX-2,and GRP78 were significantly higher in BIDC patients compared to healthy controls(P<0.05),and a positive correlation was observed among them(P<0.05).Receiver operating characteristic analysis demonstrated that FOXM1,COX-2,and GRP78 had excellent diagnostic value in predicting the occurrence of BIDC(P<0.05).Subsequently,we found significant differences in FOXM1,COX-2,and GRP78 levels among patients with different histological grades and metastasis statuses(with vs without)(P<0.05).Cox analysis revealed that FOXM1,COX-2,GRP78,increased histological grade,and the presence of tumor metastasis were independent risk factors for prognostic death in BIDC(P<0.001).CONCLUSION FOXM1,COX-2,and GRP78 exhibit abnormally high expression in BIDC,promoting malignant tumor development and closely correlating with prognosis.These findings hold significant research implications for the future diagnosis and treatment of BIDC.
基金Supported by The National Natural Science Foundation of China,No.30872482 and No.81072051
文摘AIM: To investigate the expression of forkhead box protein M1(Fox M1) in the process of epithelial mesenchymal transition in hepatocellular carcinoma(HCC) and its role in metastasis.METHODS: Fox M1 and E-cadherin expression in HCC tissue microarray specimens was evaluated by immunohistochemical staining,and statistical methods were applied to analyze the correlation between FoxM 1 and epithelial-mesenchymal transition(EMT).KaplanMeier analysis of the correlation between the Fox M1 expression level and recurrence or overall survival of HCC patients was performed.The expression of FoxM 1,E-cadherin and snail homologue 1(SNAI1) in HCC cell lines was evaluated by real-time reverse transcriptionpolymerase chain reaction and Western blot.Hepatocyte growth factor(HGF) was used to induce EMT and stimulate cell migration in HCC cells.The expression of Fox M1 and SNAI1 was regulated by transfection with plasmids pc DNA3.1 and si RNAs in vitro.The occurrence of EMT was evaluated by Transwell assay,morphologic analysis and detection of the expression of EMT markers(E-cadherin and vimentin).Luciferase and chromatin immunoprecipitation assays were used to evaluate whether SNAI1 is a direct transcriptional target of FoxM 1.RESULTS: FoxM 1 expression was increased significantly in HCC compared with para-carcinoma(10.7 ± 0.9 vs 8.2 ± 0.7,P < 0.05) and normal hepatic(10.7 ± 0.9 vs 2.7 ± 0.4,P < 0.05) tissues.Overexpression of Fox M1 was correlated with HCC tumor size,tumor number,macrovascular invasion and higher TNM stage,but was negatively correlated with E-cadherin expression in microarray specimens and in cell lines.Fox M1 overexpression was correlated significantly with HCC metastasis and EMT.In vitro,we found that FoxM 1 plays a key role in HGF-induced EMT,and overexpression of Fox M1 could suppress E-cadherin expression and induce EMT changes,which were associated with increased HCC cell invasiveness.Next,we confirmed that FOXM1 directly binds to and activates the SNAI1 promoter,and we identified SNAI1 as a direct transcriptional target of FOXM1.Moreover,inhibiting the expression of SNAI1 significantly inhibited FoxM 1-mediated EMT.CONCLUSION: Fox M1 overexpression promotes EMT and metastasis of HCC,and SNAI1 plays a critical role in FoxM 1-mediated EMT.
