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The Mechanism Of CTRP6 Regulating Proliferation,Invasion And Metastasis Of Bladder Cancer,the Correlation Analysis Of Prognosis,as Well As Clinical Characteristics And Prognostic Factors Of Metastatic Bladder Cancer

Posted on:2022-10-18Degree:DoctorType:Dissertation
Country:ChinaCandidate:X ZhuFull Text:PDF
GTID:1484306527997789Subject:Surgery
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OBJECTIVEThe CTRP gene family is widely involved in the occurrence and development of a variety of tumors.As one of the most important members of the CTRP family,the biological role of CTRP6 in bladder cancer remains unclear.This study aimed to explore expression differences of CTRP6 gene in bladder cancer cells,the effect of CTRP6 gene on the proliferation,invasion and migration of bladder cancer,and the potential mechanism.METHODSIn this study,PCR and Western blotting were used to detect and compare the gene and protein expression differences of CTRP6 in various bladder cancer cell lines,including UMUC3,T24,BIU87,5637 and normal bladder mucosal cell lines SV-HUC-1.After screening out the bladder cancer cell lines with relatively high CTRP6 expression,the expression of CTRP6 gene was further knocked down by small interfering RNA technology.The effects of CTRP6 expression on the proliferation,invasion and migration of bladder cancer cells were further explored by CCK8,plate cloning,Transwell invasion and migration assay.RESULTSCompared with normal bladder mucosal cell line SV-HUC-1,CTRP6 was highly expressed in bladder cancer cell lines including UMUC3,T24,BIU87,5637,with respect to both m RNA and protein levels.After selecting 5637 and T24 cell lines with high CTRP6 expression for further investigation,CCK8,plate cloning,Transwell invasion and migration experiments showed that cell proliferation rate was slightly reduced compared with the normal group,but the results were not statistically significant after knockdown of CTRP6 in 5637 and T24 cell lines.However,the invasion ability and migration ability of 5637 and T24 cells were significantly decreased after knockdown of CTRP6 expression,when compared with 5637 and T24 cell lines with normal expression of CTRP6,and the changes of invasion and migration ability were statistically different.CONCLUSIONBoth CTRP6 gene and protein were highly expressed in bladder cancer cell lines of UMUC3,T24,BIU87 and 5637,when compared with normal bladder mucosal cell line SV-HUC-1,and the significantly elevated expression of CTRP6 in bladder cancer cell lines was found to contribute to increased invasion and migration ability of bladder cancer.OBJECTIVEBladder cancer is one of the most common urinary malignancies.This study is aimed at providing some promising molecular biomarkers for bladder cancer by investigating the correlation between CTRP6 expression and clinical characteristics as well as prognosis in patients with bladder cancer.METHODSSequencing profiles of CTRP6 mRNA in bladder cancer patients were collected to evaluate the distinctive gene expression,between normal bladder mucosa and bladder cancer,according to the TCGA-BLCA dataset and GSE13507 dataset from GEO databases.The association between CTRP6 expressions and the clinical features as well as the disease prognosis was evaluated using the two independent cohorts.Moreover,the correlation between CTRP6 protein expressions and prognosis of bladder cancer was further evaluated by using the bladder cancer tissue microarray,composed of 54 cancer samples,combined with immunohistochemistry staining and scoring results.RESULTSCTRP6 mRNA levels were found to be differentially expressed in two independent cohorts,including the TCGA database and GSE13507 dataset from GEO.High CTRP6 expression was detected in advanced T/M stages,pathological grade,and AJCC stage when compared to the low CTRP6 expression group.The low CTRP6 expression group presented a more prominent OS advantage over the high-expression group in both TCGA and GSE13507 cohorts.Moreover,the protein content in tissues was further validated using the HPA database and TMA.Survival analyses also indicated that the high CTRP6 expression group had an unfavorable OS when compared to the low-expression group.CONCLUSIONHigh CTRP6 expression may serve as a robust indicator of poor prognosis in bladder cancer patients,and the underlying mechanism is possibly associated with changes on cancer cell migration and invasion ability.OBJECTIVELarge-scale population-based studies on primary bladder cancer with synchronous metastasis were still scarce.This study aimed to investigate the incidence,risk factors and prognosis-associated factors of bladder cancer with synchronous metastasis based on the Surveillance,Epidemiology and End Results(SEER)database.METHODSPatients diagnosed with primary bladder cancer with synchronous metastasis were stratified by specific metastatic sites,including lung,bone,liver and brain.Multivariate logistic regression was applied to identify risk factors associated with the presence of lung,bone,liver,and brain metastasis.Multivariate Cox regression was used to explore factors associated with all-cause and cancer-specific survival of metastatic bladder cancer.RESULTSPositive lymph node metastasis,muscle-invasive status,poor or undifferentiated histologic status,and unmarried social status were risk factors for lung,bone,liver and brain metastasis of bladder cancer.On multivariate Cox regression for overall survival and cancer-specific survival,only chemotherapy(vs.no chemotherapy)was the significant protective factor against all-cause and cancer-specific mortality in all the different sites of metastasis.Surgery reduced all-cause and cancer-specific mortality only in the lung metastasis and bone metastasis cohorts.Surgery of primary site was beneficial with respect to both OS and CSS for bladder cancer with lung or bone metastasis.CONCLUSIONChemotherapy was the most significant factor in determining both OS and CSS in metastatic bladder cancer.
Keywords/Search Tags:Bladder cancer, proliferation, invasion, metastasis, prognosis, overall survival, progression-free survival, chemotherapy, surgery
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