Delphan Mahmoud, Lin Tengda, Liesenfeld David B, Nattenmüller Johanna, Böhm Jürgen T, Gigic Biljana, Habermann Nina, Zielske Lin, Schrotz-King Petra, Schneider Martin, Ulrich Alexis, Kauczor Hans-Ulrich, Ulrich Cornelia M, Ose Jennifer
Huntsman Cancer Institute, Salt Lake City, UT, USA.
Department of Population Health Sciences, University of Utah, Salt Lake City, UT, USA.
Metabolomics. 2018 Mar;2018(14):22. doi: 10.1007/s11306-017-1314-8. Epub 2018 Jan 31.
Branched-chain amino acids (BCAA) have been previously linked to survival in colorectal cancer (CRC) patients. It is unclear whether BCAAs are prognostic biomarkers or surrogate markers for energy balance.
We aimed to determine correlations of BCAAs with markers of energy balance over time and to investigate prognostic significance of BCAAs in CRC.
We used urinary samples from newly diagnosed CRC patients [n=163; (stage I - IV)] from the ColoCare study in Heidelberg, Germany, collected at surgery (n=163), 6 (n=83) and 12 months follow-up (n=54). Isoleucine, leucine, valine, (2Z)-3-methylglutaconic acid (3HM), 2-ethylhydracrylic acid (2EA), 2-methyl-3-hydroxybutyrate (2M3H) were detected using gas-chromatography mass-spectrometry and proton-nuclear-magnetic-resonance spectroscopy. Partial correlation coefficients between BCAAs with body mass index (BMI), physical activity (metabolic equivalent [MET]) and muscle area were computed and adjusted for sex and age at diagnosis. We used Cox proportional hazard models to investigate overall survival (OS) after 24 months of follow-up.
We did not observe significant correlations between BCAAs and parameters of energy balance at all time points (correlation ranges: BMI: r= -0.13 to -0.01; METs: r=-0.14 to 0.02; dorsal muscle: r=-0.03 to 0.10). BCAAs were not associated with risk of death in stage I-III (e.g., valine: HR=1.62, p=0.25) or in stage IV tumors. Elevated concentrations of 2EA and 2M3H were significantly associated with OS, independent of stage (2EA: stage I-III: HR=0.42, p=0.04; stage IV: HR=0.51, p=0.01).
Our study suggests that BCAAs in colorectal cancer patients do not reflect parameters of energy balance and may be independently associated with overall survival.
支链氨基酸（BCAA）此前已被证明与结直肠癌（CRC）患者的生存情况有关。目前尚不清楚BCAAs是预后生物标志物还是能量平衡的替代标志物。
我们旨在确定BCAAs与能量平衡标志物随时间的相关性，并研究BCAAs在CRC中的预后意义。
我们使用了来自德国海德堡ColoCare研究中163例新诊断CRC患者（I - IV期）的尿液样本，这些样本分别在手术时（163例）、术后6个月（83例）和12个月随访时（54例）收集。使用气相色谱 - 质谱联用和质子核磁共振波谱法检测异亮氨酸、亮氨酸、缬氨酸、（2Z）-3-甲基戊二酸（3HM）、2-乙基氢丙烯酸（2EA）、2-甲基-3-羟基丁酸（2M3H）。计算BCAAs与体重指数（BMI）、身体活动（代谢当量[MET]）和肌肉面积之间的偏相关系数，并根据诊断时的性别和年龄进行调整。我们使用Cox比例风险模型研究随访24个月后的总生存期（OS）。
我们在所有时间点均未观察到BCAAs与能量平衡参数之间存在显著相关性（相关范围：BMI：r = -0.13至-0.01；METs：r = -0.14至0.02；背部肌肉：r = -0.03至0.10）。BCAAs与I - III期（例如，缬氨酸：HR = 1.62，p = 0.25）或IV期肿瘤的死亡风险无关。2EA和2M3H浓度升高与OS显著相关，且与分期无关（对于2EA，I - III期：HR = 0.42，p = 0.04；IV期：HR = 0.51，p = 0.01）。
我们的研究表明，结直肠癌患者体内的BCAAs不能反映能量平衡参数，且可能与总生存期独立相关。
