Evidence map›Paper›PMID 42352344›Full record

ArticleBiomolecules2026

The Exchangeable Copper-Zinc Ratio Links Sex Hormones, Tumor Burden, and Epithelial Remodeling in Colorectal Cancer.

Rosanna Squitti, Anastasia De Luca, Altea Severino, Gianluca Rizzo, Luca Emanuele Amodio, Federica Marzi, Gabriella Vicano, Mauro Cozzolino, Angela Lombardi, Mauro Rongioletti and 1 more

Abstract read
In one paragraph

Article in Biomolecules, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
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1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors.

Rosanna SquittiDepartment of Laboratory Science, Research and Development Division, Ospedale Isola Tiberina-Gemelli Isola, 00186 Rome, Italy.ORCID 0000-0002-5624-1140
Anastasia De LucaDepartment of Biology, University of Rome Tor Vergata, Via della Ricerca Scientifica 1, 00133 Roma, Italy.ORCID 0000-0002-6532-989X
Altea SeverinoDepartment of Laboratory Science, Research and Development Division, Ospedale Isola Tiberina-Gemelli Isola, 00186 Rome, Italy.
Gianluca RizzoUOC Chirurgia Digestiva e del Colon-Retto, Ospedale Isola Tiberina-Gemelli Isola, 00186 Rome, Italy.ORCID 0000-0001-6586-0472
Luca Emanuele AmodioUOC Chirurgia Digestiva e del Colon-Retto, Ospedale Isola Tiberina-Gemelli Isola, 00186 Rome, Italy.ORCID 0009-0000-1636-5766
Federica MarziUOC Chirurgia Digestiva e del Colon-Retto, Ospedale Isola Tiberina-Gemelli Isola, 00186 Rome, Italy.
Gabriella VicanoPhD Program in Cellular and Molecular Biology, Department of Biology, University of Rome Tor Vergata, Via della Ricerca Scientifica 1, 00133 Rome, Italy.
Mauro CozzolinoInstitute of Translational Pharmacology, CNR, Via Fosso del Cavaliere 100, 00133 Rome, Italy.ORCID 0000-0003-0342-8961
Angela LombardiDepartment of Theoretical and Applied Sciences, eCampus University, Viale Massenzio Masia, 26, 22100 Novedrate, Italy.
Mauro RongiolettiDepartment of Laboratory Science, Research and Development Division, Ospedale Isola Tiberina-Gemelli Isola, 00186 Rome, Italy.
Vincenzo TondoloUOC Chirurgia Digestiva e del Colon-Retto, Ospedale Isola Tiberina-Gemelli Isola, 00186 Rome, Italy.ORCID 0000-0003-0256-3766

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Copper (Cu)-zinc (Zn) imbalance has been implicated in colorectal cancer (CRC). Exchangeable copper (exCu), the labile circulating Cu fraction, may better reflect functionally relevant metal dysregulation than total Cu. We investigated sex-specific associations between systemic Cu-Zn indices, tumor burden, and epithelial-mesenchymal transition (EMT)-related tissue remodeling in CRC. We studied 152 CRC patients and 140 healthy controls. Serum Cu, Zn, and exCu were measured using validated analytical methods; circulating gonadotropins, sex steroids, and carcinoembryonic antigen were also assessed. EMT-related proteins (E-cadherin, vimentin, fibronectin, vinculin, MEMO1) were quantified by Western blot in paired tumor and adjacent mucosa. Analyses were sex-stratified and age-adjusted. CRC patients exhibited higher serum Cu and exCu and lower Zn than controls, resulting in a marked increase in the exCu:Zn ratio in both sexes. In patients, exCu:Zn was associated with tumor burden and pathological stage, with stronger associations with tumor size and pT stage in women and with metastatic status in men. Serum exCu:Zn was associated with tumor - normal differences in EMT-related proteins, particularly ΔE-cadherin, in both sexes. Systemic Cu-Zn disequilibrium, summarized by the exCu:Zn ratio, was associated with tumor burden and epithelial remodeling in CRC in a sex-specific manner, suggesting its potential as a biologically informative biomarker warranting further validation.

Indexed as

Colorectal NeoplasmsCopperGonadal Steroid HormonesZincAgedCadherinsEpithelial-Mesenchymal TransitionFemaleHumansMaleMiddle AgedTumor BurdenCadherinsCopperGonadal Steroid HormonesZinccadherincolorectal cancercoppersex hormoneszinc

Identifiers

PMID42352344
PMCPMC13297341

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.