右侧结肠癌（RCC）和左侧结肠癌（LCC）之间的肿瘤细胞代谢差异已经得到充分证实，这可能是它们在临床行为上观察到的显著差异的基础，尤其是在转移性疾病中。因此，我们利用液相色谱质谱联用技术对来源于RCC（N=32）和LCC（N=58）患者的冷冻肝转移（LM）生物库样品进行了非靶向代谢组学分析，以进一步阐明各种独特的生物学差异。我们还对一部分重叠患者的样本（RCC：N=10；LCC：N=18）进行了非靶向RNA-seq和随后的网络分析。我们的生物库再次证实了RCC来源的LM患者的较差生存率（P=0.04），这是一个经过充分确认的结果。我们的代谢组学结果显示，在RCC中出现与反应性氧化物相关的代谢产物和胆汁酸的增加。相反，在LCC中，肉碱作为脂肪酸氧化的指标相对增加。转录组分析表明RCC LM中MEK-ERK、PI3K-AKT和转录生长因子β信号通路的增加。我们的多组学分析揭示了细胞生理学的一些关键差异，这些差异综合在一起可能与RCC和LCC肝转移之间的肿瘤行为的临床差异相关。版权所有©2023，由Elsevier B.V.出版。

There are well demonstrated differences in tumor cell metabolism between right sided (RCC) and left sided (LCC) colon cancer, which could underlie the robust differences observed in their clinical behavior, particularly in metastatic disease. As such, we utilized liquid chromatography-mass spectrometry to perform an untargeted metabolomics analysis comparing frozen liver metastasis (LM) biobank samples derived from patients with RCC (N = 32) and LCC (N = 58) to further elucidate the unique biology of each. We also performed an untargeted RNA-seq and subsequent network analysis on samples derived from an overlapping subset of patients (RCC: N = 10; LCC: N = 18). Our biobank redemonstrates the inferior survival of patients with RCC-derived LM (P = 0.04), a well-established finding. Our metabolomic results demonstrate the increase of reactive oxygen species associated metabolites and bile acids in RCC. Conversely, carnitines, indicators of fatty acid oxidation, were relatively increased in LCC. The transcriptomic analysis implicated increased MEK-ERK, PI3K-AKT and Transcription Growth Factor Beta signaling in RCC LM. Our multi-omic analysis reveals several key differences in cellular physiology which taken together may be relevant to clinical differences in tumor behavior between RCC and LCC liver metastasis.Copyright © 2023. Published by Elsevier B.V.