Consistent Metabolomic and Genetic Evidence Supports Acisoga as a Key Contributor to Colorectal Neoplasia Progression

BACKGROUND: Colorectal cancer (CRC) is a leading cause of cancer incidence and mortality worldwide. Early detection and accurate risk stratification of precursor lesions remain critical challenges. Integrating metabolomics with genetic analysis may improve understanding of CRC development and identify disease determinants. METHODS: Untargeted serum metabolomics was performed in 513 individuals: 185 controls, 74 with low-, 98 with intermediate-, and 100 with high-risk lesions, and 56 CRC cases. Overall, 1,562 metabolic features were analysed using linear trend models with multiple-testing correction. Significant metabolites were further investigated through metabolite-level genome-wide association studies (GWAS). Findings were externally validated in 1,121 colon cancer-control pairs from The European Prospective Investigation into Cancer and Nutrition (EPIC) cohort and in CRC GWAS meta-analysis. RESULTS: The polyamine Acisoga showed statistically significant increasing trends across CRC progression (p=2.8×10-5). The association was independently validated in EPIC (OR=1.23, 95%CI: 1.01-1.50). Metabolite-level GWAS identified genome-wide significant loci, including OPCML, EWSAT1, CTBP2 and CMKLR1. Genetically predicted Acisoga levels were positively associated with CRC risk (p=0.003), with consistent results in sensitivity analyses using previously reported Acisoga-associated variants. CONCLUSIONS: We show a reproducible association between Acisoga and CRC progression and risk, supported by metabolomic, genetic, and external data. This integrative approach advances understanding of metabolic processes involved in CRC and supports further evaluation of Acisoga in risk research. IMPACT: This work supports Acisoga as a potential circulating biomarker for CRC risk, with implications for early detection and prevention in screening populations.

Authors

Institutions

Publication Details

Journal
Cancer Epidemiology Biomarkers & Prevention
Published
2026-05-27
DOI
https://doi.org/10.1158/1055-9965.epi-25-2050
Primary Topic
Metabolomics and Mass Spectrometry Studies
Type
article
Field-Weighted Citation Impact
0.00
Controls
|||
ALL TIME
JAN
FEB
MAR
APR
MAY
JUN
JUL
AUG
SEP
OCT
article

Consistent Metabolomic and Genetic Evidence Supports Acisoga as a Key Contributor to Colorectal Neoplasia Progression

Hwayoung Noh, Anastasia Chrysovalantou Chatziioannou, Salvatore Panico, Thérèse Truong et al.
Cancer Epidemiology Biomarkers & Prevention
Metabolomics and Mass Spectrometry Studies
article

Consistent Metabolomic and Genetic Evidence Supports Acisoga as a Key Contributor to Colorectal Neoplasia Progression

Hwayoung Noh, Anastasia Chrysovalantou Chatziioannou, Salvatore Panico, Thérèse Truong, Núria Moragas, Elisabet Guinó, Carmen Atencia, Francisco D. Morón-Duran, E Fryer, ­Rosario ­Tumino, Fulvio Ricceri, Yazdan Asgari, Saverio Caini, L. Rodriguez Alonso, Marc J. Gunter, Anne Marie Tjønneland, José María Huerta, Gianluca Severi, Valeria Pala, Raúl Zamora-Ros, Nivonirina Ranoroarivony. Robinot, Agnetha Linn. Rostgaard-Hansen, Alfredo Mata, Pekka Keski-Rahkonen, Iosu Delfrade, Victor Moreno, Ana García-Rodríguez, Mireia Obón-Santacana, Ferran Moratalla-Navarro, Mazda Jenab, Blanca Rius-Sansalvador, Maria-Jose Sánchez, Olatz Mokoroa, Gemma Ibáñez-Sanz
article en

Abstract

BACKGROUND: Colorectal cancer (CRC) is a leading cause of cancer incidence and mortality worldwide. Early detection and accurate risk stratification of precursor lesions remain critical challenges. Integrating metabolomics with genetic analysis may improve understanding of CRC development and identify disease determinants. METHODS: Untargeted serum metabolomics was performed in 513 individuals: 185 controls, 74 with low-, 98 with intermediate-, and 100 with high-risk lesions, and 56 CRC cases. Overall, 1,562 metabolic features were analysed using linear trend models with multiple-testing correction. Significant metabolites were further investigated through metabolite-level genome-wide association studies (GWAS). Findings were externally validated in 1,121 colon cancer-control pairs from The European Prospective Investigation into Cancer and Nutrition (EPIC) cohort and in CRC GWAS meta-analysis. RESULTS: The polyamine Acisoga showed statistically significant increasing trends across CRC progression (p=2.8×10-5). The association was independently validated in EPIC (OR=1.23, 95%CI: 1.01-1.50). Metabolite-level GWAS identified genome-wide significant loci, including OPCML, EWSAT1, CTBP2 and CMKLR1. Genetically predicted Acisoga levels were positively associated with CRC risk (p=0.003), with consistent results in sensitivity analyses using previously reported Acisoga-associated variants. CONCLUSIONS: We show a reproducible association between Acisoga and CRC progression and risk, supported by metabolomic, genetic, and external data. This integrative approach advances understanding of metabolic processes involved in CRC and supports further evaluation of Acisoga in risk research. IMPACT: This work supports Acisoga as a potential circulating biomarker for CRC risk, with implications for early detection and prevention in screening populations.

Cancer Epidemiology Biomarkers & Prevention
Institut Gustave Roussy (FR), Bellvitge University Hospital (ES), University of Bristol (GB), Instituto de Salud Pública de Navarra (ES), Institut d'Investigació Biomédica de Bellvitge (ES), Istituto per lo Studio e la Prevenzione Oncologica (IT), Hospital de Viladecans (ES), Biogipuzkoa Health Research Institute (ES), Centre Léon Bérard (FR), Institut Català d'Oncologia (ES), NIHR Imperial Biomedical Research Centre (GB), Instituto de Investigación Biosanitaria de Granada (ES), Associazione Italiana Di Oncologia Medica (IT), Hospital de Sant Joan Despí Moisès Broggi (ES), Danish Cancer Society (DK), Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (ES), Fondazione IRCCS Istituto Nazionale dei Tumori (IT), Centre international de recherche sur le cancer (FR), Imperial College London (GB), University of Turin (IT), University of Naples Federico II (IT)
Good health and well-being
Openalex Percentile: Top 9%
Metabolomics and Mass Spectrometry Studies
DOISourceOpenAlex
AI Navigator

Ask Laika to Summarize, Analyze, and Connect papers live on the map.

Summarize Papers & Methodologies

Extract key findings, datasets, and comparative methods across publications.

Benchmark Rankings & Visual Analytics

Rank top research institutions, authors, funders, topics, and journals by Field-Weighted Citation Impact (FWCI) and paper volume with instant charts.

Connect Distant Disciplines

Bridge topological clusters on the map to find hidden collaborative intersections.