Background:Kidney renal clear cell carcinoma(KIRC),a prevalent urological malignancy,represents about 3%of all adult malignancies.KIRC,accounting for~75%of renal malignancies,has poor prognosis in metastatic stages.Id...Background:Kidney renal clear cell carcinoma(KIRC),a prevalent urological malignancy,represents about 3%of all adult malignancies.KIRC,accounting for~75%of renal malignancies,has poor prognosis in metastatic stages.Identifying robust prognostic markers remains urgent.Block of proliferation 1(BOP1),a WD40-repeat protein,is implicated in cancer pathogenesis,but its role in KIRC is unclear.This study aimed to characterize BOP1 expression in KIRC and evaluate its prognostic value.Methods:BOP1 transcriptional levels were assessed through TCGA-KIRC RNA sequencing datasets.ROC curve construction was implemented via R statistical packages for diagnostic evaluation.Patient survival outcomes were visualized through Kaplan-Meier plotting with log-rank testing.Multivariate logistic regression models quantified associations between BOP1 expression and clinicopathological parameters.TIMER algorithm analyzed immune microenvironment composition.Genomic alterations and epigenetic modifications were investigated using cBioPortal and MethSurv platforms respectively.BOP1 protein levels in 786-O clear cell renal cell carcinoma(ccRCC)versus HK-2(normal renal)cell lines were validated by immunoblotting.Results:Evaluation of the TCGA database demonstrated that BOP1 mRNA abundance was higher in tumor specimens than in corresponding adjacent tissues.Patients with KIRC who had high BOP1 expression had differential overall survival(OS),disease-specific survival(DSS),and disease-free interval(DFI).BOP1 expression accurately recognised tumour tissues versus normal tissues(AUC=0.858),and the area under the ROCs for survival at 1,3,and 5 years were all greater than 0.6.The BOP1 gene variant rate was<1%.Out of the 15 DNA methylation CpG sites examined,7 exhibited prognostic significance in KIRC.BOP1 displayed a distinct relationship with immune cell infiltration in KIRC.The 786-O experimental group exhibited substantially higher BOP1 expression,as confirmed by Western blot detection.Conclusion:This study indicates that heightened BOP1 expression is linked to an adverse prognosis in KIRC,establishing it as an independent risk factor for this disease.These findings establish BOP1 as a novel and independent prognostic biomarker for KIRC,offering potential clinical utility for risk stratification and personalized therapeutic strategies.展开更多
目的探讨超声辐照携载短发夹RNA干扰增殖1阻断(block of proliferation1,BOP1)基因的超声微泡造影剂治疗大鼠肝纤维化的可行性。方法成功构建大鼠肝纤维化模型,将40只肝纤维化大鼠随机分为携载质粒的超声微泡组(BOP1-shRNA+US/MB)、携...目的探讨超声辐照携载短发夹RNA干扰增殖1阻断(block of proliferation1,BOP1)基因的超声微泡造影剂治疗大鼠肝纤维化的可行性。方法成功构建大鼠肝纤维化模型,将40只肝纤维化大鼠随机分为携载质粒的超声微泡组(BOP1-shRNA+US/MB)、携载质粒的常规超声组(BOP1-shRNA+US)、单纯质粒组(BOP1-shRNA)及空白对照组(CON),每组10只。BOP1-shRNA+US/MB组及BOP1-shRNA+US组分别经股静脉注入1mL微泡溶液及1mL携载单纯质粒的生理盐水后,行肝区超声辐照。所有分组大鼠在干预21d后行磁共振扩散加权成像检查后麻醉脱颈处死,取肝脏组织行苏木精-伊红(HE)染色观察病理变化。应用Western blot法检测BOP1蛋白在大鼠肝脏组织中的表达,检验BOP1的沉默效果。结果 BOP1-shRNA+US/MB组的表观弥散系数(ADC)值高于其他3组,而指数表观弥散系数(EADC)值低于其他3个组(P<0.05)。HE染色示BOP1-shRNA+US/MB组肝脏细胞排列尚整齐,汇管区纤维组织增生,见少量炎性细胞浸润,小叶结构完整,其肝纤维化程度低于其他组。Western blot结果显示BOP1-shRNA+US/MB组大鼠肝脏组织的BOP1蛋白表达敲减成功。结论超声辐照携载BOP1基因短发夹RNA的微泡造影剂可成功治疗大鼠肝纤维化,可为肝纤维化的精准靶向治疗提供新的理论依据。展开更多
基金supported by Young Talents Cultivation Program of Xianning City,the Natural Science Foundation of Hubei Province,China(No.2024AFB502)Ph.D.Start-up Funding(No.BK202413)Medical Fund(No.2023YKY04)of Hubei University of Science and Technology.
文摘Background:Kidney renal clear cell carcinoma(KIRC),a prevalent urological malignancy,represents about 3%of all adult malignancies.KIRC,accounting for~75%of renal malignancies,has poor prognosis in metastatic stages.Identifying robust prognostic markers remains urgent.Block of proliferation 1(BOP1),a WD40-repeat protein,is implicated in cancer pathogenesis,but its role in KIRC is unclear.This study aimed to characterize BOP1 expression in KIRC and evaluate its prognostic value.Methods:BOP1 transcriptional levels were assessed through TCGA-KIRC RNA sequencing datasets.ROC curve construction was implemented via R statistical packages for diagnostic evaluation.Patient survival outcomes were visualized through Kaplan-Meier plotting with log-rank testing.Multivariate logistic regression models quantified associations between BOP1 expression and clinicopathological parameters.TIMER algorithm analyzed immune microenvironment composition.Genomic alterations and epigenetic modifications were investigated using cBioPortal and MethSurv platforms respectively.BOP1 protein levels in 786-O clear cell renal cell carcinoma(ccRCC)versus HK-2(normal renal)cell lines were validated by immunoblotting.Results:Evaluation of the TCGA database demonstrated that BOP1 mRNA abundance was higher in tumor specimens than in corresponding adjacent tissues.Patients with KIRC who had high BOP1 expression had differential overall survival(OS),disease-specific survival(DSS),and disease-free interval(DFI).BOP1 expression accurately recognised tumour tissues versus normal tissues(AUC=0.858),and the area under the ROCs for survival at 1,3,and 5 years were all greater than 0.6.The BOP1 gene variant rate was<1%.Out of the 15 DNA methylation CpG sites examined,7 exhibited prognostic significance in KIRC.BOP1 displayed a distinct relationship with immune cell infiltration in KIRC.The 786-O experimental group exhibited substantially higher BOP1 expression,as confirmed by Western blot detection.Conclusion:This study indicates that heightened BOP1 expression is linked to an adverse prognosis in KIRC,establishing it as an independent risk factor for this disease.These findings establish BOP1 as a novel and independent prognostic biomarker for KIRC,offering potential clinical utility for risk stratification and personalized therapeutic strategies.
