前列腺癌患者血清TWEAK和SREBP-1水平表达与临床病理特征及无进展生存预后的关系研究

Study on the Serum TWEAK and SREBP-1 Levels in Patients with Prostate Cancer and Their Relationship with Clinical Pathological Characteristics and Progression Free Survival Prognosis

目的 研究前列腺癌(prostate cancer,PC)患者血清肿瘤坏死因子样弱凋亡诱导因子(tumor necrosis factor like weak inducer of apoptosis,TWEAK)、固醇调节元件结合蛋白1(sterol regulatory element-binding protein 1,SREBP-1)表达与临床病理特征及无进展生存预后的关系。方法 选取2018年1月~2020年1月武汉市东西湖区人民医院行PC根治术的94例PC患者为PC组,以同期50例前列腺增生(benign prostatic hyperplasia,BPH)患者为BPH组,以同期体检的50例健康人为对照组。酶联免疫吸附试验(enzyme-linked immunosorbent assay,ELISA)检测血清TWEAK和SREBP-1表达水平。Kaplan-Meier生存分析比较血清TWEAK和SREBP-1对PC患者无进展生存预后的影响。多因素COX回归分析影响PC患者无进展生存预后的因素。结果PC组患者血清TWEAK(77.14±15.46 ng/L),SREBP-1(334.14±33.81 ng/L)高于BPH组(38.69±10.58 ng/L,201.69±28.74 ng/L)和对照组(36.26±10.27 ng/L,189.51±27.65 ng/L),差异具有统计学意义(t=23.752,25.249;34.636,37.821,均P<0.05)。PC患者血清TWEAK与SREBP-1表达呈显著正相关(r=0.668,P=0.001)。Gleason评分> 7分、TNM分期Ⅲ期及术前前列腺特异抗原(prostate specific antigen,PSA)水平≥20 ng/ml的PC患者血清TWEAK,SREBP-1水平高于Gleason评分≤7分,TNM分期Ⅰ~Ⅱ期及术前PSA水平<20 ng/ml,差异具有统计学意义(t=8.465~16.597,均P<0.05)。TWEAK高表达组和低表达组三年总体无进展生存率分别为60.42%(29/48)和86.96%(40/46),SREBP-1高表达组和低表达组三年总体无进展生存率分别为57.78%(26/45)和87.76%(43/49);TWEAK高表达组、SREBP-1高表达组三年累积无进展生存率低于TWEAK低表达组、SREBP-1低表达组,差异具有统计学意义(Log-rankχ2=8.125,9.547,P=0.004,0.002)。TNM分期Ⅲ期(OR=1.448,P <0.001)、Gleason评分> 7分(OR=1.401,P <0.001)、术前PSA≥20 ng/ml (OR=1.353,P <0.001)及血清TWEAK (OR=1.338,P <0.001)和SREBP-1 (OR=1.293,P <0.001)是影响PC患者无进展生存预后的独立危险因素。结论 PC患者血清TWEAK和SREBP-1升高,两者与PC临床病理特征相关,是评估无进展生存预后的血清标志物。

Objective To investigate the serum tumor necrosis factor like weak inducer of apoptosis(TWEAK),sterol regulatory element-binding protein 1(SREBP-1)levels in patients with prostate cancer(PC)and their relationship with clinical pathological characteristics and progression free survival prognosis.Method A total of 94 PC patients who underwent PC radical surgery in Wuhan Dongxihu District People’s Hospital from January 2018 to January 2020 were selected as the PC group.Meanwhile,50 patients with benign prostatic hyperplasia(BPH)during the same period were selected as the BPH group,and 50 healthy individuals who underwent physical examination during the same period were selected as the control group.Enzyme linked immunosorbent assay(ELISA)was used to detect the expression levels of serum TWEAK and SREBP-1.Kaplan-Meier survival analysis was used to analyze the effects of serum TWEAK and SREBP-1 on the progression free survival in prostate cancer patients.Multivariate COX regression analysis was used to analyze factors affecting the prognosis of progression free survival in prostate cancer patients.Results The serum TWEAK(77.14±15.46 ng/L)and SREBP-1(334.14±33.81 ng/L)levels in the PC group were higher than those in the BPH group(38.69±10.58 ng/L,201.69±28.74 ng/L)and control group(36.26±10.27 ng/L,189.51±27.65 ng/L),with significant differences(t=23.752,25.249,34.636,37.821,all P<0.05).There was a positive correlation between serum TWEAK and SREBP-1 expression in PC patients(r=0.668,P=0.001).The serum TWEAK and SREBP-1 levels in PC patients with Gleason score>7,TNM stage III,and preoperative prostate specific antigen(PSA)level≥20 ng/ml were higher than those with Gleason score≤7,TNM stage I~II,and preoperative PSA level<20ng/ml,with significance differences(t=8.465~16.597,all P<0.05).The 3-year overall progression free survival rates of the TWEAK high expression and low expression groups were 60.42%(29/48)and 86.96%(40/46),respectively.The 3-year overall progression free survival rates of the SREBP-1 high expression and low expression groups were 57.78%(26/45)and 87.76%(43/49),respectively.The 3-year cumulative progression free survival rates of the TWEAK high expression group and the SREBP-1 high expression group were lower than those of the TWEAK low expression group and the SREBP-1 low expression group,and the differences were significant(Log rankχ2=8.125,9.547,P=0.004,0.002).TNM stage III(OR=1.448,P<0.001),Gleason score>7(OR=1.401,P<0.001),preoperative PSA≥20 ng/ml(OR=1.353,P<0.001),serum TWEAK(OR=1.338,P<0.001),and SREBP-1(OR=1.293,P<0.001)were independent risk factors affecting the progression free survival prognosis of PC patients.Conclusion Serum TWEAK and SREBP-1 in prostate cancer patients were increased,and they were correlated with the clinical pathological characteristics of PC.They could be serum biomarkers for evaluating the prognosis of progression free survival.