Body Mass Index and Metastatic Renal Cell Carcinoma: Clinical and Biological Correlations
Body Mass Index and Metastatic Renal Cell Carcinoma: Clinical and Biological Correlations
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DOI：
10.1200/jco.2016.66.7311
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发表时间：
2016-10-20
影响因子：
45.3
通讯作者：
Choueiri, Toni K.
中科院分区：
文献类型：
--
作者：
Albiges, Laurence;Hakimi, A. Ari;Choueiri, Toni K.
目的肥胖是肾透明细胞癌（RCC）的一个既定的危险因素，然而，一些报告表明，RCC发生在肥胖患者可能更惰性。我们研究了体重指数（BMI）对转移性肾细胞癌患者治疗结果的临床和生物学影响。（高BMI：>= 25 kg/m（2）v低BMI：< 25 kg/m2）对总生存期（OS）和靶向治疗的治疗结果的影响，来自国际转移性肾细胞癌数据库联盟（IMDC）的975例患者和4，657例患者的外部验证队列。还研究了癌症基因组图谱数据集中的脂肪酸代谢途径的基因表达谱，以及脂肪酸合酶（FAT 11）的免疫组织化学染色。进行考克斯回归以估计BMI与OS的相关性，并根据IMDC预后因素进行调整。（95% CI，23.2 - 28.6），高BMI患者vs 17.1个月（95% CI，15.5 - 18.5）（校正风险比，0.84; 95% CI，0.73 - 0.95）。在验证队列中，高BMI与OS改善相关（校正的风险比，0.83; 95% CI，0.74 - 0.93;中位数：分别为23.4个月[95% CI，21.9 - 25.3个月]和14.5个月[95% CI，13.8 - 15.9个月]）。在癌症基因组图谱数据集（n = 61）中，FXR基因表达与BMI呈负相关（P = 0.034），低FXR表达组的OS较长（中位数：36.8 vs 15.0个月; P = 0.002）。在IMDC不良（48%）和中等（34%）风险组中，FRENTA免疫组化阳性率比在有利风险组（17%; P趋势= 0.015）中更频繁地检测到。结论高BMI是转移性RCC患者靶向治疗后生存率和无进展生存率提高的预后因素。潜在的生物学表明Festival途径的作用。(C)2016年美国临床肿瘤学会
PurposeObesity is an established risk factor for clear cell renal cell carcinoma (RCC); however, some reports suggest that RCC developing in obese patients may be more indolent. We investigated the clinical and biologic effect of body mass index (BMI) on treatment outcomes in patients with metastatic RCC.MethodsThe impact of BMI (high BMI: >= 25 kg/m(2) v low BMI: < 25 kg/m(2)) on overall survival (OS) and treatment outcome with targeted therapy was investigated in 1,975 patients from the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) and in an external validation cohort of 4,657 patients. Gene expression profiling focusing on fatty acid metabolism pathway, in The Cancer Genome Atlas data set, and immunohistochemistry staining for fatty acid synthase (FASN) were also investigated. Cox regression was undertaken to estimate the association of BMI with OS, adjusted for the IMDC prognostic factors.ResultsIn the IMDC cohort, median OS was 25.6 months (95% CI, 23.2 to 28.6) in patients with high BMI versus 17.1 months (95% CI, 15.5 to 18.5) in patients with low BMI (adjusted hazard ratio, 0.84; 95% CI, 0.73 to 0.95). In the validation cohort, high BMI was associated with improved OS (adjusted hazard ratio, 0.83; 95% CI, 0.74 to 0.93; medians: 23.4 months [95% CI, 21.9 to 25.3 months] v 14.5 months [95% CI, 13.8 to 15.9 months], respectively). In The Cancer Genome Atlas data set (n = 61), FASN gene expression inversely correlated with BMI (P = .034), and OS was longer in the low FASN expression group (medians: 36.8 v 15.0 months; P = .002). FASN immunohistochemistry positivity was more frequently detected in IMDC poor (48%) and intermediate (34%) risk groups than in the favorable risk group (17%; P-trend = .015).ConclusionHigh BMI is a prognostic factor for improved survival and progression-free survival in patients with metastatic RCC treated with targeted therapy. Underlying biology suggests a role for the FASN pathway. (C) 2016 by American Society of Clinical Oncology