Metabolomics profiling of visceral and abdominal subcutaneous adipose tissue in colorectal cancer patients: results from the ColoCare study
Metabolomics profiling of visceral and abdominal subcutaneous adipose tissue in colorectal cancer patients: results from the ColoCare study
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DOI：
10.1007/s10552-020-01312-1
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发表时间：
2020-05-19
影响因子：
2.3
通讯作者：
Ulrich, Cornelia M.
中科院分区：
文献类型：
--
作者：
Ose, Jennifer;Holowatyj, Andreana N.;Ulrich, Cornelia M.
目的 身体脂肪与结直肠癌之间关系的潜在机制仍不清楚。本研究调查了结直肠癌患者循环代谢物与内脏 (VFA)、腹部皮下 (SFA) 和总脂肪面积 (TFA) 的关联。方法 使用来自 ColoCare 研究的 212 名患者（I-IV 期）的术前血浆样本进行靶向代谢组学分析。 VFA、SFA 和 TFA 通过计算机断层扫描进行量化。计算并校正了 VFA、SFA 和 TFA 与代谢物的偏相关和线性回归分析，以进行多重测试。 Cox 比例风险用于评估 2 年生存率。结果 在转移性肿瘤患者中，SFA 和 TFA 与 16 种甘油磷脂呈显着负相关（SFA：p(FDR) 范围 0.017-0.049；TFA：p(FDR) 范围 0.029-0.048），而 VFA 则不然。上述十种甘油磷脂的加倍与转移性肿瘤患者的死亡风险增加相关，但与非转移性肿瘤患者无关（p(het)范围：0.00044-0.049）。 PC ae C34:0 加倍与转移性肿瘤死亡风险增加九倍相关（风险比 [HR], 9.05；95% 置信区间 [CI] 2.17-37.80）；在非转移性肿瘤中观察到负相关（HR 0.17；95% CI 0.04-0.87；p(het) = 0.00044）。结论 这些数据提供了初步证据，证明转移性结直肠癌中的甘油磷脂与皮下肥胖独特相关，并可能影响总生存期。
Purpose Underlying mechanisms of the relationship between body fatness and colorectal cancer remain unclear. This study investigated associations of circulating metabolites with visceral (VFA), abdominal subcutaneous (SFA), and total fat area (TFA) in colorectal cancer patients. Methods Pre-surgery plasma samples from 212 patients (stage I-IV) from the ColoCare Study were used to perform targeted metabolomics. VFA, SFA, and TFA were quantified by computed tomography scans. Partial correlation and linear regression analyses of VFA, SFA, and TFA with metabolites were computed and corrected for multiple testing. Cox proportional hazards were used to assess 2-year survival. Results In patients with metastatic tumors, SFA and TFA were statistically significantly inversely associated with 16 glycerophospholipids (SFA: p(FDR) range 0.017-0.049; TFA: p(FDR) range 0.029-0.048), while VFA was not. Doubling of ten of the aforementioned glycerophospholipids was associated with increased risk of death in patients with metastatic tumors, but not in patients with non-metastatic tumors (p(het) range: 0.00044-0.049). Doubling of PC ae C34:0 was associated with ninefold increased risk of death in metastatic tumors (Hazard Ratio [HR], 9.05; 95% confidence interval [CI] 2.17-37.80); an inverse association was observed in non-metastatic tumors (HR 0.17; 95% CI 0.04-0.87; p(het) = 0.00044). Conclusion These data provide initial evidence that glycerophospholipids in metastatic colorectal cancer are uniquely associated with subcutaneous adiposity, and may impact overall survival.