The ability of bilirubin in identifying smokers with higher risk of lung cancer: a large cohort study in conjunction with global metabolomic profiling.
The ability of bilirubin in identifying smokers with higher risk of lung cancer: a large cohort study in conjunction with global metabolomic profiling.
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DOI：
10.1158/1078-0432.ccr-14-0748
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发表时间：
2015-01-01
期刊：
影响因子：
--
通讯作者：
Wu X
中科院分区：
文献类型：
--
作者：
Wen CP;Zhang F;Liang D;Wen C;Gu J;Skinner H;Chow WH;Ye Y;Pu X;Hildebrandt MA;Huang M;Chen CH;Hsiung CA;Tsai MK;Tsao CK;Lippman SM;Wu X
我们的目的是确定血清代谢物作为肺癌潜在的有价值的生物标志物，并改善吸烟者的风险分层。我们进行了整体代谢组学分析，然后在 386 例肺癌病例和 193 例匹配对照的病例对照设计中对个体代谢物进行了针对性验证。然后，我们在一个由 425,660 名参与者组成的大型前瞻性队列中验证了胆红素作为肺癌发病率和死亡率的风险标志物的情况，胆红素在病例和对照中始终显示出显着的差异水平。通过整体代谢组学分析和随后的针对性验证，健康对照和肺癌病例之间的胆红素水平始终显示出统计学上的显着差异。在前瞻性队列中，无论吸烟年限和吸烟强度如何，仅在男性吸烟者中观察到负相关。与胆红素最高组（>1 mg/dL）的男性吸烟者相比，胆红素最低组（<0.75 mg/dL）的男性吸烟者肺癌发病率和死亡率分别增加55%和66%。胆红素每降低 0.1 mg/dL，男性吸烟者肺癌发病率和死亡率的风险分别增加 5% 和 6%（均 P < 0.001）。低血清胆红素水平与吸烟对肺癌风险存在显着的交互作用（交互作用 P = 0.001）。血清胆红素水平低与男性吸烟者肺癌发病率和死亡率较高的风险相关，可用于识别肺癌风险较高的吸烟者。
We aimed to identify serum metabolites as potential valuable biomarkers for lung cancer and to improve risk stratification in smokers. We performed global metabolomic profiling followed by targeted validation of individual metabolites in a case-control design of 386 lung cancer cases and 193 matched controls. We then validated bilirubin, which consistently showed significant differential levels in cases and controls, as a risk marker for lung cancer incidence and mortality in a large prospective cohort comprised of 425,660 participants. Through global metabolomic profiling and following targeted validation, bilirubin levels consistently showed a statistically significant difference among healthy controls and lung cancer cases. In the prospective cohort, the inverse association was only seen in male smokers, regardless of smoking pack-years and intensity. Compared with male smokers in the highest bilirubin group (>1 mg/dL), those in the lowest bilirubin group (<0.75 mg/dL) had 55% and 66% increase in risks of lung cancer incidence and mortality, respectively. For every 0.1 mg/dL decrease of bilirubin, the risks for lung cancer incidence and mortality increased by 5% and 6% in male smokers, respectively (both P < 0.001). There was a significant interaction between low serum bilirubin level and smoking on lung cancer risk (P for interaction = 0.001). Low levels of serum bilirubin are associated with higher risks of lung cancer incidence and mortality in male smokers and can be used to identify higher risk smokers for lung cancer.