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Integrated Spatial and Bulk Untargeted Metabolomics Characterize Location- and Histology-Associated Metabolic
Junfeng Wang1, Jinjin Gao1, Jia Liu1
1Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Key Laboratory of Digestive Cancer, Tianjin300060, China.
Journal of Proteome Research
|June 29, 2026
Summary
Colorectal cancer (CRC) shows molecular differences based on tumor location. This study explored spatial metabolomics, finding distinct metabolic profiles in left-sided colon cancer versus right-sided colon cancer, influenced by histology.
Area of Science:
- Oncology
- Metabolomics
- Cancer Research
Background:
- Colorectal cancer (CRC) displays significant molecular heterogeneity.
- Assessing spatial metabolic differences is challenging due to interindividual variability.
- Tumor location and histology are key factors in CRC progression.
Purpose of the Study:
- To investigate spatial metabolomic differences in colorectal cancer.
- To explore the influence of primary tumor location and histology on metabolic architecture.
- To minimize genetic confounding by studying synchronous tumors from a single patient.
Main Methods:
- Exploratory single-case spatial metabolomics (MALDI-MSI) on synchronous bilateral tumors.
- Untargeted metabolomics (UHPLC-HRMS/MS) on tumor and matched normal tissues from 30 CRC patients.
- Analysis of metabolite distribution from tumor core to invasive margin.
Main Results:
- Left-sided colon cancer (LCC) showed distinct metabolite distribution compared to right-sided colon cancer (RCC).
- In tubular adenocarcinomas, LCC was enriched in ether lipid and phosphatidylcholine metabolism, while RCC favored nucleotide and fatty acid metabolism.
- Right-sided mucinous adenocarcinomas exhibited unique sphingolipid alterations, suggesting a shift from apoptosis to structural functions.
Conclusions:
- Primary tumor location and histology significantly influence the microenvironmental metabolic architecture in colorectal cancer.
- Metabolic profiles differ between LCC and RCC, with distinct associations to histological subtypes.
- Findings provide exploratory insights into location- and histology-dependent tumor adaptation for future research.
