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硬脂酰辅酶A去饱和酶1的高表达预示着透明细胞肾细胞癌患者的预后不良。

High Expression of Stearoyl-CoA Desaturase 1 Predicts Poor Prognosis in Patients with Clear-Cell Renal Cell Carcinoma.

作者信息

Wang Jianfeng, Xu Yunze, Zhu Liangsong, Zou Yun, Kong Wen, Dong Baijun, Huang Jiwei, Chen Yonghui, Xue Wei, Huang Yiran, Zhang Jin

机构信息

Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.

出版信息

PLoS One. 2016 Nov 18;11(11):e0166231. doi: 10.1371/journal.pone.0166231. eCollection 2016.

Abstract

Stearoyl-CoA desaturase 1 (SCD1), the rate-limiting enzymes in the biosynthesis of monounsaturated fatty acids from saturated fatty acids, have been gradually recognized as a potential therapeutic target for various malignancies, particularly in clear-cell renal cell carcinoma (ccRCC). However, the prognostic value of SCD1 in ccRCC is still unknown. The aim of this study is to evaluate the clinical significance of SCD1 expression in patients with ccRCC. SCD1 expression in tumor tissues obtained from 359 patients who underwent nephrectomy for ccRCC are retrospectively assessed. During a median follow-up of 63 months (range: 1-144month), 56 patients in total died before the last follow-up in this study. Survival curves were plotted with the Kaplan-Meier method and compared with the log-rank test. Meanwhile, univariate and multivariate Cox regression models were applied to evaluate the prognostic value of SCD1 expression in overall survival (OS) for ccRCC patients. Moreover, SCD1 was enrolled into a newly built nomogram with factors selected by multivariate analysis, and the calibration was built to evaluate the predictive accuracy of nomogram. High SCD1 expression occurred in 61.6% (221/359) of ccRCC patients, which was significantly associated with age (p = 0.030), TNM stage (p = 0.021), pN stage (p = 0.014), Fuhrman grade (p = 0.014) and tumor sizes (p = 0.040). In multivariate analysis, SCD1 expression was confirmed as an adverse independent prognostic factor for OS. The prognostic accuracy of TNM stage, Fuhrman grade and tumor sizes was significantly increased when SCD1 expression was added. The independent prognostic factors, pT stage, pN stage, Fuhrman grade and tumor sizes, as well as SCD1 expression were integrated to establish a predictive nomogram with high predictive accuracy. Calibration curves revealed optimal consistency between observations and prognosis. In conclusion, high SCD1 expression is an independent prognostic factor for OS in patients with ccRCC. Our data suggest that the expression of SCD1 might guide the clinical decisions for patients with ccRCC.

摘要

硬脂酰辅酶A去饱和酶1(SCD1)是将饱和脂肪酸生物合成单不饱和脂肪酸的限速酶,已逐渐被认为是各种恶性肿瘤的潜在治疗靶点,尤其是在透明细胞肾细胞癌(ccRCC)中。然而,SCD1在ccRCC中的预后价值仍不清楚。本研究的目的是评估SCD1表达在ccRCC患者中的临床意义。回顾性评估了359例因ccRCC接受肾切除术患者的肿瘤组织中SCD1的表达情况。在中位随访63个月(范围:1 - 144个月)期间,本研究中共有56例患者在最后一次随访前死亡。采用Kaplan - Meier法绘制生存曲线,并通过对数秩检验进行比较。同时,应用单因素和多因素Cox回归模型评估SCD1表达对ccRCC患者总生存期(OS)的预后价值。此外,将SCD1纳入通过多因素分析选择的因素构建的新列线图中,并构建校准曲线以评估列线图的预测准确性。61.6%(221/359)的ccRCC患者出现高SCD1表达,这与年龄(p = 0.030)、TNM分期(p = 0.021)、pN分期(p = 0.014)、Fuhrman分级(p = 0.014)和肿瘤大小(p = 0.040)显著相关。在多因素分析中,SCD1表达被确认为OS的不良独立预后因素。当加入SCD1表达时,TNM分期、Fuhrman分级和肿瘤大小的预后准确性显著提高。将独立预后因素pT分期、pN分期、Fuhrman分级、肿瘤大小以及SCD1表达整合起来,建立了具有高预测准确性的预测列线图。校准曲线显示观察结果与预后之间具有最佳一致性。总之,高SCD1表达是ccRCC患者OS的独立预后因素。我们的数据表明,SCD1的表达可能指导ccRCC患者的临床决策。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/55b0/5115711/5a287832dc00/pone.0166231.g001.jpg

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