1.Mechanism of translationally-controlled tumor protein 1 in regulating proliferation and migration of renal cell carcinoma cells
Qingqing WANG ; Xinzhong HUANG ; Yinyu HU ; Jie CAO
Academic Journal of Naval Medical University 2024;45(12):1521-1528
Objective To detect the expression of translationally-controlled tumor protein 1(TPT1)in renal cell carcinoma(RCC)and to explore its role in RCC.Methods Microarray dataset GSE15641(including 23 normal kidney tissue samples and 32 RCC tissue samples)was downloaded from the Gene Expression Omnibus,and differentially expressed genes between RCC tissue and normal kidney tissue were screened using R 4.3.0 software.The TPT1 expression in RCC tissue and adjacent non-tumor tissue of 90 patients diagnosed and treated at Affiliated Hospital of Nantong University,as well as in human RCC cells(769-P,786-O,ACHN,and Caki-1)and human embryonic kidney 293 cell(HEK293)was detected by quantitative polymerase chain reaction(qPCR)and Western blotting.The relationship between TPT1 expression and clinical pathological characteristics of RCC patients was analyzed by χ2 test.The clinical data of 522 RCC patients were derived from The Cancer Genome Atlas,and the correlation between TPT1 expression and prognosis of RCC patients was analyzed by receiver operating characteristic(ROC)curve and Kaplan-Meier survival curve.After in vitro transfection of TPT1 small interfering RNA(siRNA)and its negative control(NC)into 786-O and Caki-1 cells,the TPT1 expression was detected by qPCR and Western blotting;the proliferation,migration,and invasion were detected by cell counting kit 8 assay,scratch assay,and Transwell assay,respectively;and the expression of apoptosis-related proteins was detected by Western blotting.Results TPT1 expression was significantly upregulated in the RCC tissue and cells compared with the normal kidney tissue and HEK293 cells(all P<0.05).The RCC patients with low TPT1 expression levels had significantly smaller tumor size and lower metastasis rate than those with high TPT1 expression levels(both P<0.05).The ROC curve analysis results indicated that TPT1 had high diagnostic value for RCC(area under curve was 0.856 9,95%confidence interval was 0.804 5-0.909 3,P<0.001).The Kaplan-Meier survival analysis results showed that the overall survival of RCC patients in the low TPT1 expression group was significantly longer than that in the high TPT1 expression group(P=0.018 4).In the cell experiment,compared with the siRNA NC group,the proliferation activity,scratch healing rate,and invading transmembrane cell number of 786-O and Caki-1 cells were significantly decreased after transfection with TPT1 siRNA(all P<0.01);the expression levels of B-lymphoma gene 2(Bcl-2)and matrix metalloproteinase-9 were significantly decreased,while the expression of Bcl-2 associated X protein was significantly increased(all P<0.05).Conclusion TPT1 is involved in the progression of RCC and may be a potential therapeutic target for RCC.
2.Relationships of serum angiopoietin-like protein 4 and fibroblast growth factor 23 levels with severity and prognosis of patients with diabetes nephropathy
Lele HU ; Yinyu WEI ; Jinyan WANG ; Kunliang ZHU ; Guoying LIU
Journal of Clinical Medicine in Practice 2024;28(18):56-61
Objective To investigate the relationships of serum angiopoietin-like protein 4(ANGPTL4)and fibroblast growth factor-23(FGF-23)levels with the severity and prognosis of patients with diabet-ic nephropathy.Methods A total of 120 patients(diabetic nephropathy group)with diabetic nephrop-athy were selected from July 2018 to July 2020 and divided into mild group(n=62)and severe group(n=58)according to the staging criteria of diabetic nephropathy;based on the prognosis within 3 years,they were also divided into good prognosis group(n=94)and poor prognosis group(n=26).Addition-ally,102 diabetic patients were enrolled as diabetic group,and 81 healthy volunteers were selected as control group.The serum levels of ANGPTL4 and FGF-23 in diabetic nephropathy patients were detected by enzyme-linked immunosorbent assay(ELISA).Logistic regression analysis was used to analyze the influencing factors of prognosis,and receiver operating characteristic(ROC)curves were drawn to ana-lyze the values of ANGPTL4,FGF-23 and their combination in assessing the severity and prognosis of diabetic nephropathy.Results The levels of ANGPTL4 and FGF-23 in the diabetic nephropathy group and simple diabetic group were significantly higher than those in the control group(P<0.05);compared with the simple diabetic group,the levels of ANGPTL4 and FGF-23 in the diabetic ne-phropathy group were significantly increased(P<0.05);the levels of ANGPTL4 and FGF-23 in the severe group were significantly higher than those in the mild group(P<0.05);the ROC curve analysis revealed that the areas under the curve(AUCs)for assessing disease severity of ANGPTL4,FGF-23 and their combination were 0.748,0.781 and 0.858 respectively,and the combined diagnosis was significantly better than FGF-23(Z=2.149,P=0.032)and ANGPTL4(Z=2.886,P=0.004)alone;the levels of ANGPTL4 and FGF-23 in the good prognosis group were significantly lower than those in the poor prognosis group(P<0.05);significant differences were observed in diabetes dura-tion,blood urea nitrogen(BUN),serum creatinine(Scr),fasting blood glucose(FBG),glycated hemoglobin(HbA1C),hypertension,ANGPTL4 and FGF-23 levels between diabetic nephropathy pa-tients with different prognoses(P<0.05);the Scr,ANGPTL4 and FGF-23 levels were all risk factors affecting the prognosis of diabetic nephropathy(P<0.05);the ROC curve analysis for prognosis as-sessment showed that the AUCs of ANGPTL4,FGF-23 and their combination were 0.774,0.795 and 0.874 respectively;the combined diagnosis was significantly better than FGF-23(Z=2.385,P=0.171)and ANGPTL4(Z=2.317,P=0.021)alone.Conclusion The serum levels of ANGPTL4 and FGF-23 are significantly increased in diabetic nephropathy patients,and they have certain refer-ence value for the clinical diagnosis and prognosis assessment of diabetic nephropathy patients.
3.Relationships of serum angiopoietin-like protein 4 and fibroblast growth factor 23 levels with severity and prognosis of patients with diabetes nephropathy
Lele HU ; Yinyu WEI ; Jinyan WANG ; Kunliang ZHU ; Guoying LIU
Journal of Clinical Medicine in Practice 2024;28(18):56-61
Objective To investigate the relationships of serum angiopoietin-like protein 4(ANGPTL4)and fibroblast growth factor-23(FGF-23)levels with the severity and prognosis of patients with diabet-ic nephropathy.Methods A total of 120 patients(diabetic nephropathy group)with diabetic nephrop-athy were selected from July 2018 to July 2020 and divided into mild group(n=62)and severe group(n=58)according to the staging criteria of diabetic nephropathy;based on the prognosis within 3 years,they were also divided into good prognosis group(n=94)and poor prognosis group(n=26).Addition-ally,102 diabetic patients were enrolled as diabetic group,and 81 healthy volunteers were selected as control group.The serum levels of ANGPTL4 and FGF-23 in diabetic nephropathy patients were detected by enzyme-linked immunosorbent assay(ELISA).Logistic regression analysis was used to analyze the influencing factors of prognosis,and receiver operating characteristic(ROC)curves were drawn to ana-lyze the values of ANGPTL4,FGF-23 and their combination in assessing the severity and prognosis of diabetic nephropathy.Results The levels of ANGPTL4 and FGF-23 in the diabetic nephropathy group and simple diabetic group were significantly higher than those in the control group(P<0.05);compared with the simple diabetic group,the levels of ANGPTL4 and FGF-23 in the diabetic ne-phropathy group were significantly increased(P<0.05);the levels of ANGPTL4 and FGF-23 in the severe group were significantly higher than those in the mild group(P<0.05);the ROC curve analysis revealed that the areas under the curve(AUCs)for assessing disease severity of ANGPTL4,FGF-23 and their combination were 0.748,0.781 and 0.858 respectively,and the combined diagnosis was significantly better than FGF-23(Z=2.149,P=0.032)and ANGPTL4(Z=2.886,P=0.004)alone;the levels of ANGPTL4 and FGF-23 in the good prognosis group were significantly lower than those in the poor prognosis group(P<0.05);significant differences were observed in diabetes dura-tion,blood urea nitrogen(BUN),serum creatinine(Scr),fasting blood glucose(FBG),glycated hemoglobin(HbA1C),hypertension,ANGPTL4 and FGF-23 levels between diabetic nephropathy pa-tients with different prognoses(P<0.05);the Scr,ANGPTL4 and FGF-23 levels were all risk factors affecting the prognosis of diabetic nephropathy(P<0.05);the ROC curve analysis for prognosis as-sessment showed that the AUCs of ANGPTL4,FGF-23 and their combination were 0.774,0.795 and 0.874 respectively;the combined diagnosis was significantly better than FGF-23(Z=2.385,P=0.171)and ANGPTL4(Z=2.317,P=0.021)alone.Conclusion The serum levels of ANGPTL4 and FGF-23 are significantly increased in diabetic nephropathy patients,and they have certain refer-ence value for the clinical diagnosis and prognosis assessment of diabetic nephropathy patients.