肾周脂肪解偶联蛋白1表达对肾透明细胞癌患者预后的影响

Increased UCP1 mRNA expression of perirenal fat predicts a poor prognosis of clear cell renal cell carcinoma

目的评估肾周脂肪解耦连蛋白1(UCP1)表达对肾透明细胞癌(ccRCC)患者预后的影响。方法选取2013年2月至10月及2015年3月至10月收治的行后腹腔镜根治性肾切除术的ccRCC患者共98例,通过术前CT图像评估肾周脂肪厚度及黏连度。术后RT-qPCR检测肿瘤周围肾周脂肪UCP1,依据肾周脂肪UCP1 mRNA值,将患者分成高UCP1表达组(42例)与低UCP1组表达组(56例)。比较两组患者的一般临床资料、肾周脂肪厚度及黏连度,进一步采用Kaplan-Meier曲线评估两组间无进展生存期(PFS)的差异。采用单变量和多变量Cox回归分析确定PFS的潜在独立预后因素。结果高UCP1表达组的肾周脂肪厚度、肾周脂肪黏连比例、Fuhrman分级中Ⅲ~Ⅳ级比例和T分期中>T2期比例高于低UCP1表达组[(13.84±2.41)vs(10.75±1.99),42.86%vs 16.07%,28.57%vs 8.93%,21.43%vs 5.36%;P值分别为0.000,0.003,0.011,0.037]。随访期间(中位时间62.0个月),15例患者(12例高UCP1表达组,3例低UCP1表达组)发生肿瘤进展。Kaplan-Meier曲线显示,高UCP1表达组较低UCP1表达组PFS更差(71.43%vs 94.64%,P=0.001)。Cox回归分析显示,高UCP1表达和高T分期与低PFS显著相关(β=1.334,RR=3.796,95%CI=1.009~14.280,P=0.048;β=2.886,RR=17.930,95%CI=5.538~58.047,P=0.000)。结论肾周脂肪UCP1表达增加可能为ccRCC患者肿瘤进展的独立危险因素。术后联合肾周脂肪棕色化评估可能有助于临床更好的判断ccRCC患者的预后。

Objective To evaluate the effect of uncoupling protein 1(UCP1)expression of perirenal fat on the prognosis of clear cell renal cell carcinoma(ccRCC).Methods From Feb.2013 to Oct.2013 and Mar.2015 to Oct.2015,98 patients with ccRCC who underwent retroperitoneal laparoscopic radical nephrectomy were analyzed.UCP1 mRNA of perirenal fat around tumor was detected by RT-qPCR.Preoperative Computed tomography(CT)images were used to evaluate the thickness and adhesiveness of perirenal fat.According to the UCP1 mRNA value,the patients were divided into high UCP1 group(42 cases)and low UCP1 group(56 cases).The general clinical data,perirenal fat thickness and adhesiveness were compared,and Kaplan Meier curve was used to evaluate the difference of progression free survival(PFS)between the two groups.Univariate and multivariate Cox analysis were used to determine the potential independent prognostic factors of PFS.Results In the high UCP1 group,the renal fat thickness,the ratio of fat adhesion,the ratio ofⅢtoⅣin Fuhrman grade and the ratio of>T2 in T stage were higher than those in the low UCP1 group[(13.84±2.41)vs(10.75±1.99),42.86%vs 16.07%,28.57%vs 8.93%,21.43%vs.5.36%;P=0.000,P=0.003,P=0.011,P=0.037].During the follow-up period(median,62.0 months),15 cases(12 cases of high UCP1 group,3 case of low UCP1 group)developed tumor progression.Kaplan Meier curve showed that PFS of high UCP1 group was worse than that of low UCP1 group(71.43%vs 94.64%,P=0.001).Cox regression analysis showed that high UCP1 expression and high T stage were significantly correlated with low PFS(β=1.334,RR=3.796,95%CI=1.009-14.280,P=0.048;β=2.886,RR=17.930,95%CI=5.538-58.047,P=0.000).Conclusions The increased UCP1 expression of perirenal fat may be an independent risk factor of tumor progression in ccRCC.Combined with the assessment of browning of perirenal adipose tissue may be helpful for risk stratification of ccRCC patients after surgery.