Joint prognostic effect of obesity and chronic systemic inflammation in patients with metastatic colorectal cancer.
Joint prognostic effect of obesity and chronic systemic inflammation in patients with metastatic colorectal cancer.
复制标题
肥胖症和慢性全身性炎症对转移性结直肠癌患者的关节预后作用。
DOI：
10.1002/cncr.29440
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发表时间：
2015-09-01
期刊：
影响因子：
6.2
通讯作者：
Daniel CR
中科院分区：
文献类型：
--
作者：
Shah MS;Fogelman DR;Raghav KP;Heymach JV;Tran HT;Jiang ZQ;Kopetz S;Daniel CR
肥胖与慢性全身性炎症密切相关，每一种都与结直肠癌（CRC）的进展和生存有关。我们研究了肥胖和循环细胞因子对转移性结直肠癌（mCRC）的联合预后影响，这是一个研究不足的患者组。在242例未经化疗的mCRC患者中，我们测量了多种细胞因子，并从病历中提取了临床病理特征、身高和体重。计算从诊断日期至全因死亡日期的总生存期（OS），并通过Kaplan-Meier分析和多变量考克斯比例风险回归模型进行评价。通过限制性三次样条回归确定细胞因子的切割点。在多变量模型中，白细胞介素（IL）-8、IL-2受体α和乳酸脱氢酶（LDH）升高是OS不良的显著预测因素[高于结点与低于结点（参考）的风险比（HR）和95%置信区间（CI）：2.5（1.7，3.7）; 1.9（1.3，2.7）;和2.2（1.6，3.1）;所有P<0.001]。肥胖（BMI>30）与OS无关，但似乎改变了观察到的与IL-8和LDH的关系，与非肥胖患者的2倍死亡风险相比，肥胖患者的死亡风险显著增加4倍和5倍（P-相互作用分别= 0.06和0.04）。关节效应分析也出现了类似的结果，其中IL-8（或LDH）高的肥胖患者死亡风险最高。虽然肥胖本身与mCRC患者的生存率无关，但LDH和IL-8的不良预后重要性在肥胖患者中增强。
Obesity is strongly linked with chronic systemic inflammation, and each has been linked with progression and survival in colorectal cancer (CRC). We investigated the joint prognostic effects of obesity and circulating cytokines in metastatic CRC (mCRC), an understudied patient group. In 242 chemotherapy naïve mCRC patients, we measured a multiplex cytokine panel and abstracted clinical-pathological features, height, and weight from medical records. Overall survival (OS) was calculated from the date of diagnosis until the date of death from any cause and evaluated by Kaplan-Meier analysis and multivariable Cox proportional hazards regression models. Cut points for cytokines were determined by restricted cubic spline regression. In multivariable models, elevated interleukin (IL)-8, IL-2 receptor alpha and lactate dehydrogenase (LDH) emerged as significant predictors of poor OS [hazard ratio (HR) and 95% confidence interval (CI) for above vs. below (ref) knot point: 2.5 (1.7, 3.7); 1.9 (1.3, 2.7); and 2.2 (1.6, 3.1), respectively; all P<0.001]. Obesity (BMI>30) was not associated with OS, but appeared to modify the relationships observed with IL-8 and LDH, which were associated with a significant 4- and 5-fold risk of death in obese patients, as compared to a 2-fold risk of death in non-obese patients (P-interaction= 0.06 and 0.04, respectively). Similar results emerged from joint effects analysis, where obese patients with high IL-8 (or LDH) experienced the highest risk of death. Although obesity itself was not independently associated with survival in mCRC patients, the adverse prognostic importance of LDH and IL-8 was enhanced in obese patients.