Exometabolome and Molecular Signatures Associated with HPV 16 in Cervical Cancer - Integrative Metabolomic and Transcriptomic Analysis for Biomarker Discovery

Sep 23, 2026

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Cervical cancer is a major global public health burden, driven by persistent infection with high-risk human papillomaviruses, with HPV 16 implicated in more than half of cases. This work profiles the exometabolome of HPV 16-positive SiHa and Ca Ski cell lines and an HPV 16-negative control (C-33A). Exometabolic measurements are validated by transcriptomic molecular signatures, followed by 1H-NMR and multivariate/univariate statistics. The analysis leverages GEO GSE9750 to identify distinct metabolic gene and pathway shifts, supporting non-invasive diagnostic and prognostic biomarkers and therapeutic targets.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages22

Reading Time55 min

AccessFree to download

Introduction

Exometabolomic profiling approach

Transcriptomic molecular signatures

Statistical comparison of cell lines

GSE9750-based molecular signature analysis

Article Exometabolome and Molecular Signatures Associated with HPV 16 in Cervical Cancer: Integrative Metabolomic and Transcriptomic Analysis for Biomarker Discovery Adán Arizmendi-Izazaga 1, Napoleón Navarro-Tito 2, Gabriela Elizabeth Campos-Viguri 3, Hilda Jiménez-Wences 1,4,5, Macdiel Emilio Acevedo-Quiroz 6, Eric Genaro Salmerón-Bárcenas 7, Berenice Illades-Aguiar 8, Marco Antonio Leyva-Vázquez 8 and Julio Ortiz-Ortiz 1, * Academic Editor: Qian Chen Received: 24 July 2025 Revised: 10 September 2025 Accepted: 22 September 2025 Published: 28 September 2025 Citation: Arizmendi-Izazaga, A.; Navarro-Tito, N.; Campos-Viguri, G.E.; Jiménez-Wences, H.; Acevedo-Quiroz, M.E.; Salmerón-Bárcenas, E.G.; Illades-Aguiar, B.; Leyva-Vázquez, M.A.; Ortiz-Ortiz, J. Exometabolome and Molecular Signatures Associated with HPV 16 in Cervical Cancer: Integrative Metabolomic and Transcriptomic Analysis for Biomarker Discovery. Molecules 2025, 30, 3909 . [https://doi.org/10.3390/](https://doi.org/10.3390/)[ ](https://doi.org/10.3390/)molecules30193909 Copyright: © 2025 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://creativecommons.org/](https://creativecommons.org/)[ ](https://creativecommons.org/)[licenses/by/4.0/](licenses/by/4.0/)) . 1 Laboratorio de Investigación en Metabolismo y Cáncer, Facultad de Ciencias Químico Biológicas, Universidad Autónoma de Guerrero, Av. Lázaro Cárdenas S/N, Ciudad Universitaria, Colonia La Haciendita, Chilpancingo 39090, Guerrero, Mexico; [adanarizmendi@uagro.mx](adanarizmendi@uagro.mx) (A.A.-I.); [wences2009@hotmail.com](wences2009@hotmail.com) (H.J.-W.) 2 Laboratorio de Biología Celular del Cáncer, Facultad de Ciencias Químico Biológicas, Universidad Autónomade Guerrero, Av. Lázaro Cárdenas S/N, Ciudad Universitaria, Colonia La Haciendita, Chilpancingo 39090, Guerrero, Mexico; [nnavarro@uagro.mx](nnavarro@uagro.mx) 3 Centro de Investigación en Ciencia Aplicada y Tecnología Avanzada Unidad Morelos, Instituto Politécnico Nacional, Boulevard de la Tecnología, 1036 Z-1, P 2/2, Atlacholoaya 62790, Morelos, Mexico; [gabyirugiv@gmail.com](gabyirugiv@gmail.com) 4 Laboratorio de Investigación en Biomoléculas, Facultad de Ciencias Químico Biológicas, Universidad Autónoma de Guerrero, Av. Lázaro Cárdenas S/N, Ciudad Universitaria, Colonia La Haciendita, Chilpancingo 39090, Guerrero, Mexico 5 Laboratorio de Investigación en Enfermedades Infecciosas y Cáncer, Facultad de Ciencias Químico Biológicas, Universidad Autónoma de Guerrero, Av. Lázaro Cárdenas S/N, Ciudad Universitaria, Colonia La Haciendita, Chilpancingo 39090, Guerrero, Mexico 6 Department of Chemical and Biochemical Engineering, National Technological Institute of Mexico, Technological/IT Institute of Zacatepec, Zacatepec 62780, Morelos, Mexico; [macdiel.aq@zacatepec.tecnm.mx](macdiel.aq@zacatepec.tecnm.mx) 7 Departamento de Biomedicina Molecular, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Ciudad de México 07360, Mexico; [eric.salmeron@cinvestav.mx](eric.salmeron@cinvestav.mx) 8 Laboratorio de Biomedicina Molecular, Facultad de Ciencias Químico Biológicas, Universidad Autónoma de Guerrero, Av. Lázaro Cárdenas S/N, Ciudad Universitaria, Colonia La Haciendita, Chilpancingo 39090, Guerrero, Mexico; [b.illadesaguiar@gmail.com](b.illadesaguiar@gmail.com) (B.I.-A.); [leyvamarco13@gmail.com](leyvamarco13@gmail.com) (M.A.L.-V.) * [Correspondence: julioortiz@uagro.mx](Correspondence: julioortiz@uagro.mx); Tel.: +52-747-471-0901 Abstract Cervical cancer (CC) represents a major public health concern, ranking as the fourth most frequently diagnosed cancer and one of the leading causes of cancer-related mortality among middle-aged women worldwide. CC is caused by persistent infection with high-risk human papillomaviruses (HR-HPVs), with HPV 16 being

FAQs

What biological material and cell models were analyzed?

The study evaluated the exometabolome of HPV 16-positive SiHa and Ca Ski cell lines and compared them with the HPV 16-negative control cell line C-33A.

How were molecular signatures validated in the analysis?

Exometabolome results were validated using molecular signatures derived from a transcriptomic approach, focusing on genes encoding cellular metabolic enzymes.

Which experimental and analytical methods supported biomarker discovery?

Metabolomic profiling used 1H nuclear magnetic resonance spectroscopy (1H-NMR), and differences between cell lines were assessed with both multivariate and univariate statistical analyses, complemented by transcriptomic analysis from GEO dataset GSE9750.

Sep 23, 2026

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