Cohort Study of Fatty Acid Synthase Expression and Patient Survival in Colon Cancer
Cohort Study of Fatty Acid Synthase Expression and Patient Survival in Colon Cancer
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DOI：
10.1200/jco.2009.22.8858
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发表时间：
2008-12-10
影响因子：
45.3
通讯作者：
Fuchs, Charles S.
中科院分区：
文献类型：
--
作者：
Ogino, Shuji;Nosho, Katsuhiko;Fuchs, Charles S.
目的能量平衡似乎在结肠癌的发病机制中很重要。脂肪酸合酶（FASN）在生理上受能量平衡调节，并且在结直肠癌中经常上调。尽管如此，FASN 表达对患者预后的影响尚不确定。患者和方法使用两项独立队列研究中 647 例结肠癌患者的数据库，通过免疫组织化学在 84 个肿瘤 (13%) 中检测到 FASN 过度表达。 Cox 比例风险模型计算了结肠癌特异性死亡率和总体死亡率的风险比 (HR)，并根据患者特征和相关肿瘤特征进行调整，包括 KRAS、BRAF、p53、微卫星不稳定性和 CpG 岛甲基化表型。结果共有 279 例死亡，其中 160 例结肠癌特异性死亡。单变量和多变量分析显示，FASN 过表达与结肠癌特异性死亡率显着降低相关（调整后 HR，0.41；95% CI，0.19 至 0.89），并且总体死亡率改善趋势不显着（调整后 HR，0.75；95% CI，0.50 至 1.13）。值得注意的是，FASN 表达对死亡率的影响可能因体重指数（BMI；P（交互作用）= .019）而异； BMI 小于 27.5 kg/m(2) 的患者中，FASN 过度表达的总死亡率调整后 HR 为 0.63（95% CI，0.39 至 1.02），BMI >= 27.5 kg/m(2) 的患者中，FASN 过度表达的总体死亡率调整后 HR 为 2.91（95% CI，1.19 至 7.12）。此外，中度超重/肥胖对总生存期的不利影响仅限于 FASN 阳性肿瘤（调整后 HR，4.10；95% CI，1.14 至 14.8；BMI >= 27.5 kg/m(2) v < 27.5 kg/m(2)）。肥胖患者（BMI >= 27.5 kg/m(2)），FASN 过度表达可能预示更差的结果。
PurposeEnergy balance seems to be important in the pathogenesis of colon cancer. Fatty acid synthase (FASN) is physiologically regulated by energy balance and is often upregulated in colorectal cancer. Nonetheless, the influence of FASN expression on patient outcome is uncertain.Patients and MethodsUsing the database of 647 patients with colon cancer in two independent cohort studies, FASN overexpression was detected in 84 tumors (13%) by immunohistochemistry. Cox proportional hazards models calculated hazard ratios (HRs) of colon cancer-specific and overall mortalities, adjusted for patient characteristics and related tumoral features, including KRAS, BRAF, p53, microsatellite instability and the CpG island methylation phenotype.ResultsThere were 279 deaths, including 160 colon cancer-specific deaths. FASN overexpression was associated with a significant reduction in colon cancer-specific mortality by both univariate and multivariate analyses (adjusted HR, 0.41; 95% CI, 0.19 to 0.89) and an insignificant trend toward improved overall mortality (adjusted HR, 0.75; 95% CI, 0.50 to 1.13). Notably, the effect of FASN expression on mortality might be different according to body mass index (BMI; P(interaction) = .019); the adjusted HR of overall mortality for FASN overexpression was 0.63 (95% CI, 0.39 to 1.02) among patients with BMI less than 27.5 kg/m(2) and 2.91 (95% CI, 1.19 to 7.12) among those with BMI >= 27.5 kg/m(2). Moreover, the adverse effect of moderate overweight/obesity on overall survival was limited to FASN-positive tumors (adjusted HR, 4.10; 95% CI, 1.14 to 14.8; BMI >= 27.5 kg/m(2) v < 27.5 kg/m(2)).ConclusionAmong nonobese patients with colon cancer, tumoral FASN overexpression is associated with improved survival, whereas among moderately overweight or obese patients (BMI >= 27.5 kg/m(2)), FASN overexpression may predict a worse outcome.