PO.PR01.04 · 预防研究

未经治疗的早发性与晚发性结直肠癌患者中体力活动的代谢组学特征：ColoCare研究的结果

Metabolomic signatures of physical activity in treatment-naive patients with early-onset vs. late-onset colorectal cancer: Results from the ColoCare Study

编号 3627 展板 13 时间 4/20 02:00–05:00 区域 Section 36 主讲 Victoria Bandera, MS

分会场 Metabolism and Microbiome in Cancer Initiation and Prevention

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作者与单位 Authors & Affiliations

Victoria Maria Bandera¹, Tengda Lin¹, Patricia Erickson¹, Caroline Himbert¹, Aik Choon Tan¹, Mary C. Playdon¹, Alan Maschek², Paul Stewart¹, Sheetal Hardikar¹, Elaine M. Glenny³, Jennifer Ose⁴, Victoria Damerell⁵, Christy A. Warby¹, Olena Aksonova¹, Oliver Fiehn⁶, Kenneth Boucher², Peter Schirmacher⁵, Ildiko Strehli¹, Megan Mclaws¹, Alejandro Sanchez¹, Jolanta Jedrzkiewicz¹, Lyen C. Huang¹, Vaia Florou¹, Jessica N. Cohan¹, Alexander Brobeil⁵, Hans-Ulrich Kauczor⁵, Christoph Kahlert⁵, Meghana Karchi⁷, Elizabeth H. Wood⁷, Doratha A. Byrd⁸, Erin M. Siegel⁸, Adetunji T. Toriola⁹, David Shibata¹⁰, Christopher I. Li¹¹, Jane C. Figueiredo¹², Biljana Gigic⁵, Jatin Roper¹³, Stephen Hursting³, Cornelia M. Ulrich¹

¹University of Utah Huntsman Cancer Institute, Salt Lake City, UT,²University of Utah, Salt Lake City, UT,³University of North Carolina at Chapel Hill, Chapel Hill, NC,⁴University of Applied Sciences and Arts, Hannover, Germany,⁵Heidelberg University Hospital (UKHD), Heidelberg, Germany,⁶Professor, University of California, Davis, Davis, CA,⁷University of Tennessee Health Science Center, Memphis, TN,⁸Moffitt Cancer Center, Tampa, FL,⁹Washington University School of Medicine in St. Louis, St. Louis, MO,¹⁰Assoc. Professor of Surgical Onc., Div. of Interdiscipl. Onc., University of Tennessee Health Science Center - Memphis, Memphis, TN,¹¹Fred Hutchinson Cancer Center, Seattle, WA,¹²Samuel Oschin Comprehensive Cancer Institute, Los Angeles, CA,¹³Duke University, Durham, NC

摘要 Abstract

中文摘要

引言：新兴研究将体力活动不足与早发性结直肠癌（EOCRC）联系起来，但大多数研究依赖于体力活动（PA）的主观测量。代谢物特征可能提供一种客观的PA测量方法，同时也能捕捉对活动的全身代谢反应。我们在近期确诊的结直肠癌（CRC）患者中评估了一个先前经验证的PA代谢组学特征，并比较了EOCRC（<50岁）患者与非EOCRC（>50岁）患者之间的特征评分。方法：我们检查了ColoCare研究中来自亨茨曼癌症研究所（犹他州）和海德堡大学医院（德国）的122名I-III期CRC患者的基线（术前）数据。采用国际体力活动问卷简表测量前一年的PA。在西海岸代谢组学中心对非靶向血清代谢物和复杂脂质进行了分析。我们计算了一个在超过6,000名无癌个体中开发的24代谢物PA特征（Papadimitriou等，CEBP，2025），该特征由酰基肉碱、甘油磷脂、单糖、氨基酸和鞘脂组成。在代谢物预处理、归一化和标度之后，我们对数据集中可用的20种代谢物进行了多变量线性回归，校正年龄、性别、肿瘤分期和体重指数（BMI）。通过将归一化的代谢物浓度乘以先前开发的PA代谢物特征系数，为每位参与者计算代谢物评分，然后在EOCRC与非EOCRC幸存者之间进行比较。结果：与非EOCRC患者（67±9岁，N=102）相比，EOCRC患者（39±10岁，N=20）确诊时分期更高（55%对43%为III期）、肥胖BMI的患病率更低（25%对37%），且体力活动更多（16±17代谢当量（MET）小时/周对11±17 MET小时/周），p>0.05。与非EOCRC患者相比，EOCRC患者更可能达到PA指南要求（每周>150分钟中到高强度PA；60%对38%），p>0.05。在我们数据中调查的20种代谢物中，有15种与先前开发的PA特征呈现一致的关联方向。EOCRC患者的PA代谢物特征评分（0.04±0.09）高于年长患者（-0.01±0.10），t=2.3，p=0.03。在校正分期、性别和BMI后，这一适度关联仍然显著（beta=0.05，p=0.048）。结论：PA代谢物特征在我们的CRC幸存者队列中显示出与问卷来源PA测量相当的关联，这与健康个体中的发现一致。与非EOCRC患者相比，EOCRC患者报告了更高水平的PA，并具有显著更高的PA代谢物特征评分。对PA的代谢物反应可能有助于阐明体力活动不足如何影响EOCRC的风险和结局。

查看英文原文 English abstract

Introduction : Emerging studies link physical inactivity to early-onset colorectal cancer (EOCRC), but most rely on subjective measures of physical activity (PA). Metabolite signatures may offer an objective measure of PA that also captures the systemic metabolic response to activity. We assessed a previously validated PA metabolomic signature in patients with recently diagnosed colorectal cancer (CRC) and compared profile scores between patients with EOCRC (<50 yrs) vs. non-EOCRC ( > 50 yrs). Methods: We examined baseline (pre-surgery) data from 122 stage I-III patients with CRC in the ColoCare Study at Huntsman Cancer Institute (Utah) and Heidelberg University Hospital (Germany). PA for the previous year was measured with the International Physical Activity Questionnaire-Short Form. Untargeted serum metabolites and complex lipids were profiled at the West Coast Metabolomics Center. We calculated a 24-metabolite PA signature developed in >6,000 cancer-free individuals (Papadimitriou et al., CEBP, 2025) consisting of acylcarnitines, glycerophospholipids, monosaccharides, amino acids, and sphingolipids. Following metabolite pre-processing, normalization, and scaling, we performed multivariable linear regression on 20 metabolites available in our dataset, adjusting for age, sex, tumor stage, and body mass index (BMI). Metabolite scores were calculated for each participant by multiplying normalized metabolite concentrations by the previously developed PA metabolite signature coefficients and were then compared between EOCRC vs. non-EOCRC survivors. Results : Compared to patients with non-EOCRC (67±9 years, N=102), those with EOCRC (39±10 years, N=20) were diagnosed with higher stages (55% vs. 43% stage III), had lower prevalence of obese BMI (25% vs. 37%), and were more physically active (16±17 metabolic equivalent (MET) hrs/week vs. 11±17 MET hrs/week), p>0.05. Patients with EOCRC were more likely to meet PA guidelines ( > 150 min/week of moderate to vigorous PA; 60% vs. 38%) compared to those with non-EOCRC, p>0.05. Among the 20 metabolites investigated in our data, 15 showed a consistent direction of association with the previously developed PA signature. Patients with EOCRC had higher scores of the PA metabolite signature (0.04±0.09) than older patients (-0.01±0.10), t=2.3, p=0.03. This modest association remained significant after adjustment for stage, sex, and BMI (beta=0.05, p=0.048). Conclusions : A PA metabolite signature showed comparable associations to questionnaire-derived PA measures in our CRC survivor cohort, consistent with findings in healthy individuals. Patients with EOCRC reported a higher level of PA compared to those with non-EOCRC and had a significantly higher PA metabolite signature score. The metabolite response to PA may clarify how physical inactivity influences EOCRC risk and outcomes.

利益披露 Disclosure

V. M. Bandera, None.. T. Lin, None.. P. Erickson, None.. C. Himbert, None.. A. Tan, None.. M. C. Playdon, None.. A. Maschek, None.. P. Stewart, None.. S. Hardikar, None.. E. M. Glenny, None.. J. Ose, None.. V. Damerell, None.. C. A. Warby, None.. O. Aksonova, None.. O. Fiehn, None.. K. Boucher, None.. P. Schirmacher, None.. I. Strehli, None.. M. Mclaws, None.. A. Sanchez, None.. J. Jedrzkiewicz, None.. L. C. Huang, None.. V. Florou, None.. J. N. Cohan, None.. A. Brobeil, None.. H. Kauczor, None.. C. Kahlert, None.. M. Karchi, None.. E. H. Wood, None.. D. A. Byrd, None.. E. M. Siegel, None.. A. T. Toriola, None.. D. Shibata, None.. C. I. Li, None.. J. C. Figueiredo, None.. B. Gigic, None.. J. Roper, None.. S. Hursting, None.. C. M. Ulrich, None.

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