{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T05:38:46Z","timestamp":1793425126405,"version":"4.5.0"},"reference-count":53,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2025,9,28]],"date-time":"2025-09-28T00:00:00Z","timestamp":1759017600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"SEP-CONACYT","award":["CB-2017-2018 A1-S-43704"],"award-info":[{"award-number":["CB-2017-2018 A1-S-43704"]}]}],"content-domain":{"domain":["www.mdpi.com"],"crossmark-restriction":true},"short-container-title":["Molecules"],"abstract":"<jats:p>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 the cause of more than 50% of CC cases. In this study, the exometabolome of the HPV 16-positive cell lines SiHa and Ca Ski, as well as the HPV 16-negative control cell line C-33 A, was evaluated. The exometabolome was validated through molecular signatures using a transcriptomic approach to identify genes encoding cellular metabolic enzymes. The exometabolome was analyzed using 1H nuclear magnetic resonance spectroscopy (1H-NMR). Exometabolomic profiles were subsequently compared through both multivariate and univariate statistical analyses to identify significant differences between cell lines. Molecular signatures were analyzed from the GSE9750 dataset obtained from the GEO database. Exometabolic profiling of the HPV 16 positive cell lines showed higher concentrations of leucine, isoleucine, valine, lysine, methionine, glutamine, ornithine, choline, glucose, and tryptophan. An expression analysis showed increased expression of enzymes involved in amino acid synthesis, the tricarboxylic acid cycle, glycolysis, the pentose phosphate pathway, galactose metabolism, and HIF-1\u03b1. These data suggest metabolites and metabolism-associated genes that can be used as non-invasive, stable diagnostic and prognostic biomarkers, as well as therapeutic targets for CC in the presence of HPV 16.<\/jats:p>","DOI":"10.3390\/molecules30193909","type":"journal-article","created":{"date-parts":[[2025,9,29]],"date-time":"2025-09-29T12:59:46Z","timestamp":1759150786000},"page":"3909","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Exometabolome and Molecular Signatures Associated with HPV 16 in Cervical Cancer: Integrative Metabolomic and Transcriptomic Analysis for Biomarker Discovery"],"prefix":"10.3390","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4068-3312","authenticated-orcid":false,"given":"Ad\u00e1n","family":"Arizmendi-Izazaga","sequence":"first","affiliation":[{"name":"Laboratorio de Investigaci\u00f3n en Metabolismo y C\u00e1ncer, Facultad de Ciencias Qu\u00edmico Biol\u00f3gicas, Universidad Aut\u00f3noma de Guerrero, Av. L\u00e1zaro C\u00e1rdenas S\/N, Ciudad Universitaria, Colonia La Haciendita, Chilpancingo 39090, Guerrero, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4911-0545","authenticated-orcid":false,"given":"Napole\u00f3n","family":"Navarro-Tito","sequence":"additional","affiliation":[{"name":"Laboratorio de Biolog\u00eda Celular del C\u00e1ncer, Facultad de Ciencias Qu\u00edmico Biol\u00f3gicas, Universidad Aut\u00f3noma de Guerrero, Av. L\u00e1zaro C\u00e1rdenas S\/N, Ciudad Universitaria, Colonia La Haciendita, Chilpancingo 39090, Guerrero, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8674-3953","authenticated-orcid":false,"given":"Gabriela Elizabeth","family":"Campos-Viguri","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n en Ciencia Aplicada y Tecnolog\u00eda Avanzada Unidad Morelos, Instituto Polit\u00e9cnico Nacional, Boulevard de la Tecnolog\u00eda, 1036 Z-1, P 2\/2, Atlacholoaya 62790, Morelos, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1116-8733","authenticated-orcid":false,"given":"Hilda","family":"Jim\u00e9nez-Wences","sequence":"additional","affiliation":[{"name":"Laboratorio de Investigaci\u00f3n en Metabolismo y C\u00e1ncer, Facultad de Ciencias Qu\u00edmico Biol\u00f3gicas, Universidad Aut\u00f3noma de Guerrero, Av. L\u00e1zaro C\u00e1rdenas S\/N, Ciudad Universitaria, Colonia La Haciendita, Chilpancingo 39090, Guerrero, Mexico"},{"name":"Laboratorio de Investigaci\u00f3n en Biomol\u00e9culas, Facultad de Ciencias Qu\u00edmico Biol\u00f3gicas, Universidad Aut\u00f3noma de Guerrero, Av. L\u00e1zaro C\u00e1rdenas S\/N, Ciudad Universitaria, Colonia La Haciendita, Chilpancingo 39090, Guerrero, Mexico"},{"name":"Laboratorio de Investigaci\u00f3n en Enfermedades Infecciosas y C\u00e1ncer, Facultad de Ciencias Qu\u00edmico Biol\u00f3gicas, Universidad Aut\u00f3noma de Guerrero, Av. L\u00e1zaro C\u00e1rdenas S\/N, Ciudad Universitaria, Colonia La Haciendita, Chilpancingo 39090, Guerrero, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Macdiel Emilio","family":"Acevedo-Quiroz","sequence":"additional","affiliation":[{"name":"Department of Chemical and Biochemical Engineering, National Technological Institute of Mexico, Technological\/IT Institute of Zacatepec, Zacatepec 62780, Morelos, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric Genaro","family":"Salmer\u00f3n-B\u00e1rcenas","sequence":"additional","affiliation":[{"name":"Departamento de Biomedicina Molecular, Centro de Investigaci\u00f3n y de Estudios Avanzados del Instituto Polit\u00e9cnico Nacional, Ciudad de M\u00e9xico 07360, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3937-335X","authenticated-orcid":false,"given":"Berenice","family":"Illades-Aguiar","sequence":"additional","affiliation":[{"name":"Laboratorio de Biomedicina Molecular, Facultad de Ciencias Qu\u00edmico Biol\u00f3gicas, Universidad Aut\u00f3noma de Guerrero, Av. 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