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. 2026 Jan;56(1):e70157.
doi: 10.1111/eci.70157. Epub 2025 Dec 7.

Adipose tissue metabolomics identifies disease stage and tumour invasiveness of rectal cancer

Lidia Cornejo Fernández  1   2   3 , Laura Gallardo-Nuell  4   5   6 , Anna Pigem Rodeja  1   2   3   7 , Irma Ramos-Oliver  8 , Olga Delisau-Puig  1   7 , Eloi Maldonado-Marcos  1   7 , José Ignacio Rodríguez-Hermosa  1   2   3   9 , Ramon Farrés Coll  1   2   3   7 , Antoni Codina-Cazador  1 , Jordi Mayneris-Perxachs  4   5   6 , José Manuel Fernández-Real  2   3   4   5   10 , Pere Planellas Giné  1   2   3   7
Affiliations

Adipose tissue metabolomics identifies disease stage and tumour invasiveness of rectal cancer

Lidia Cornejo Fernández et al. Eur J Clin Invest. 2026 Jan.

Abstract

Backgorund: Adipose tissue has emerged as a prognostic factor in rectal cancer (RC), yet its metabolic role in tumour progression remains poorly understood. This study aims to characterise the metabolic profiles of subcutaneous (SAT) and visceral adipose tissue (VAT) in early and advanced tumours to investigate metabolic alterations that may influence tumour progression. Understanding these alterations could provide insights into mechanisms of rectal cancer and identify therapeutic targets.

Methods: Global metabolic profiles of 68 SAT and VAT samples from patients with RC were analyzed using high-performance chemical isotope labeling liquid chromatography mass spectrometry. Statistical analyses were stratified by clinical tumour invasion and disease stage.

Results: VAT exhibited distinct metabolic signatures between early and advanced tumour invasion. Advanced tumours (cT3-4) had a higher concentration of N-glycolylneuraminic acid and phenylacetylglutamine, whereas early invasive tumours (cT2) exhibited higher levels of dipeptides. Pathway enrichment analyses revealed dysregulations in taurine and hypotaurine metabolism, alanine, aspartate and glutamate metabolism, propanoate metabolism and cellular signalling pathways in advanced invasion. Propanoate metabolism emerged as a key pathway distinguishing early and advanced invasion stages. In SAT, metabolic changes aligned with overall disease stage. Early-stage disease was associated with a higher concentration of dipeptides, whereas advanced stages showed increased N-acetyl-agmatine and N-acetyl-L-noradrenaline.

Conclusions: Our study highlights significant metabolic alterations in adipose tissue associated with rectal cancer progression. VAT metabolism reflects tumour invasiveness, while SAT is more indicative of disease stage. Propanoate metabolism may serve as a biomarker for advanced invasion, offering potential for improved staging, reclassification and personalised therapeutic strategies.

Keywords: adipose tissue; metabolome; rectal cancer; tumour progression.

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References

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