Aluminum Concentration Is Associated with Tumor Mutational Burden and the Expression of Immune Response Biomarkers in Colorectal Cancers

Sep 21, 2026

Uploaded by Theodora

Environmental pollution presents a substantial public health hazard, driven in part by the bioaccumulation of aluminum (Al). This study assessed whether Al bioaccumulation in colorectal cancer (CRC) samples exerts mutagenic effects and reshapes cancer progression mediators, including immune response biomarkers. Aluminum levels were quantified in 20 CRC biopsy samples by ICP-MS, showing detection in all cases, with Al correlating to tumor mutation burden. RNA sequencing further linked Al concentration to increased CTLA-4 expression, alongside trends involving PD-1/PD-L1 and relationships with myeloid cells and IFNγ, suggesting roles in genetic mutation and immune evasion. Results emphasized the need for stricter Al exposure regulation.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages15

Reading Time38 min

AccessFree to download

Abstract

Introduction

Environmental pollution and toxic metals

Sources and routes of aluminum exposure

Article Aluminum Concentration Is Associated with Tumor Mutational Burden and the Expression of Immune Response Biomarkers in Colorectal Cancers Rita Bonfiglio 1,†, Erica Giacobbi 1,†, Valeria Palumbo 1, Stefano Casciardi 2, Renata Sisto 2, Francesca Servadei 1, Maria Paola Scioli 1, Stefania Schiaroli 1, Elena Cornella 1, Giulio Cervelli 1, Giuseppe Sica 3, Eleonora Candi 1, Gerry Melino 1, Alessandro Mauriello 1, * and Manuel Scimeca 1, * Citation: Bonfiglio, R.; Giacobbi, E.; Palumbo, V.; Casciardi, S.; Sisto, R.; Servadei, F.; Scioli, M.P.; Schiaroli, S.; Cornella, E.; Cervelli, G.; et al. Aluminum Concentration Is Associated with Tumor Mutational Burden and the Expression of Immune Response Biomarkers in Colorectal Cancers. Int. J. Mol. Sci. 2024, 25, 13388. [https://doi.org/](https://doi.org/)[ ](https://doi.org/)[10.3390/ijms252413388](10.3390/ijms252413388) Academic Editor: Zoltán Wiener Received: 30 October 2024 Revised: 10 December 2024 Accepted: 11 December 2024 Published: 13 December 2024 Copyright: © 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) . 1 Department of Experimental Medicine, Tor Vergata Oncoscience Research (TOR), University of Rome“Tor Vergata”, 00133 Rome, Italy; rita.bonfiglio@uniroma2.it (R.B.); erica.giacobbi@gmail.com (E.G.); [valeria.palumbo95@hotmail.com](valeria.palumbo95@hotmail.com) (V.P.); [francescaservadei@gmail.com](francescaservadei@gmail.com) (F.S.); [sciolimp@hotmail.it](sciolimp@hotmail.it) (M.P.S.); [schiaroli@yahoo.com](schiaroli@yahoo.com) (S.S.); [candi@uniroma2.it](candi@uniroma2.it) (E.C.) 2 Department of Occupational and Environmental Medicine, Epidemiology and Hygiene, INAIL Research, Monte Porzio Catone, 00078 Rome, Italy; [s.casciardi@inail.it](s.casciardi@inail.it) (S.C.); [r.sisto@inail.it](r.sisto@inail.it) (R.S.) 3 Department of Surgery, Tor Vergata Oncoscience Research (TOR), University of Rome “Tor Vergata”, 00133 Rome, Italy * Correspondence: [alessandro.mauriello@uniroma2.it](alessandro.mauriello@uniroma2.it) (A.M.); [manuel.scimeca@uniroma2.it](manuel.scimeca@uniroma2.it) (M.S.); Tel.: +39-20903915 (M.S.) † These authors contributed equally to this work. Abstract: Environmental pollution poses a significant risk to public health, as demonstrated by the bioaccumulation of aluminum (Al) in colorectal cancer (CRC) . This study aimed to investigate the potential mutagenic effect of Al bioaccumulation in CRC samples, linking it to the alteration of key mediators of cancer progression, including immune response biomarkers. Aluminum levels in 20 CRC biopsy samples were analyzed using inductively coupled plasma mass spectrometry (ICP-MS) . The results indicated that Al bioaccumulation occurred in 100% of the cases. A correlation between Al levels and tumor mutation burden was observed. Furthermore, RNA sequencing revealed a significant association between Al concentration and the expression of the immune checkpoint molecule CTLA-4 . Although correlations with PD-1 and PD-L1 were not statistically significant, a trend was observed. Additionally, a correlation between Al levels and both the presence of myeloid cells and IFNγ expression was detected, linking Al exposure to inflammatory responses within the tumor microenvironment. These findings suggested that Al can play a role in CRC progression by promoting both genetic mutations and immune evasion. Given the ubiquitous presence of Al in industrial and consumer products, dietary sources, and environmental pollutants, these results underscored the need for stricter regulatory measures to control Al exposure. Keywords: aluminum; colorectal cancer; immune escape; immune checkpoint; IFNγ; myeloid cells;

FAQs

How was aluminum concentration measured in colorectal cancer samples?

Aluminum levels in 20 CRC biopsy samples were analyzed using inductively coupled plasma mass spectrometry (ICP-MS).

What did the study find regarding the relationship between aluminum and tumor mutation burden?

A correlation was observed between aluminum levels and tumor mutation burden.

Which immune response biomarker was significantly associated with aluminum concentration?

RNA sequencing showed a significant association between aluminum concentration and CTLA-4 expression.

Sep 21, 2026

Uploaded by Theodora