{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T23:18:49Z","timestamp":1785453529645,"version":"3.56.0"},"reference-count":48,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T00:00:00Z","timestamp":1776988800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012226","name":"Fundamental Research Funds for the Central Universities, Peking Union Medical College","doi-asserted-by":"publisher","award":["3332024023"],"award-info":[{"award-number":["3332024023"]}],"id":[{"id":"10.13039\/501100012226","id-type":"DOI","asserted-by":"publisher"}]},{"award":["3332024023"],"award-info":[{"award-number":["3332024023"]}],"id":[{"id":"https:\/\/ror.org\/02drdmm93","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82404574"],"award-info":[{"award-number":["82404574"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"award":["82404574"],"award-info":[{"award-number":["82404574"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"name":"CAMS Innovation Fund for Medical Sciences","award":["2025-I2M-XHCL-014"],"award-info":[{"award-number":["2025-I2M-XHCL-014"]}]},{"name":"Noncommunicable Chronic Diseases\u2014National Science and Technology Major Project","award":["2024ZD0533200"],"award-info":[{"award-number":["2024ZD0533200"]}]},{"name":"Noncommunicable Chronic Diseases\u2014National Science and Technology Major Project","award":["2024ZD0533203"],"award-info":[{"award-number":["2024ZD0533203"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Metabolites"],"abstract":"<jats:p>Background\/Objectives: Colorectal cancer (CRC) is a leading cause of cancer-related mortality, with colorectal liver metastasis (CRLM) being the major determinant of poor prognosis. Tumor metabolic reprogramming and spatial heterogeneity complicate biomarker discovery and clinical management. This study aimed to characterize the spatial metabolomic landscape of CRC and identify progression-associated metabolic alterations and potential metabolic signatures for liver metastasis. Methods: A total of 23 tissue samples were collected from patients with CRC, with and without liver metastasis. Air flow-assisted desorption electrospray ionization mass spectrometry imaging (AFADESI-MSI) was used to map the spatial metabolite distributions. Region-of-interest analysis guided by histopathology enabled comparative metabolomic profiling across different tissue types. Multivariate statistical analysis, pathway enrichment, and receiver operating characteristic (ROC) curve analyses were performed to identify key metabolic alterations and evaluate potential biomarker performance. Results: Distinct spatial metabolomic profiles were observed across normal mucosa, primary tumors, liver metastases, and normal liver tissues. In primary colorectal tumors, amino acid, purine, and choline metabolism were significantly upregulated, whereas liver metastases were characterized by elevated levels of triglycerides, diglycerides, cholesteryl esters, and acylcarnitines, indicating enhanced lipid synthesis, incomplete fatty acid oxidation, and\/or mitochondrial dysfunction. Progression-associated analyses across tissue types revealed consistently increasing trends in glycerides and acylcarnitines, along with heterogeneous alterations in amino acids and phospholipids. Furthermore, 122 differential metabolites were identified between metastatic and non-metastatic CRC, and a four-lipid panel demonstrated strong discriminatory performance. Conclusions: This study provides a spatially resolved characterization of metabolic reprogramming during CRC progression and liver metastasis, highlighting lipid and amino acid metabolism as key features and revealing the metabolic signatures of CRLM.<\/jats:p>","DOI":"10.3390\/metabo16050293","type":"journal-article","created":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T14:28:23Z","timestamp":1777040903000},"page":"293","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Spatially Resolved Metabolomic Profiling Reveals Progression-Associated Metabolic Reprogramming in Colorectal Liver Metastasis"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6858-1911","authenticated-orcid":false,"given":"Ying","family":"Zhu","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-8028-9200","authenticated-orcid":false,"given":"Yixuan","family":"Cai","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qianyu","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanchuan","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qianqian","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingshi","family":"Xiang","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Songlin","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"Qiu","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China"},{"name":"State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,24]]},"reference":[{"key":"ref_1","first-page":"229","article-title":"Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA Cancer J. 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