{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T04:59:42Z","timestamp":1785214782585,"version":"3.55.0"},"reference-count":91,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,7,26]],"date-time":"2026-07-26T00:00:00Z","timestamp":1785024000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>Cervical cancer (CC) affects women worldwide, and more than 95% of cases are caused by persistent infection with high-risk human papillomavirus (HR-HPV), such as type 16, which promotes the progression of precancerous lesions to cancer. This study aimed to identify differentially expressed proteins (DEPs) in biopsies from patients with HPV16+ low-grade squamous intraepithelial lesions (LSILs) and from patients with HPV16+ squamous cell carcinoma (SCC) compared with those from HPV-negative normal cervical tissue (NCT HPV\u2212) controls. The samples were analyzed by high-performance liquid chromatography\u2013tandem mass spectrometry (HPLC-MS\/MS) using a data-independent acquisition (DIA) approach. Data processing and differential protein expression analysis were performed with the DIA-NN software (Data-Independent Acquisition Neural Networks), followed by bioinformatics analyses, including Venn diagrams, pathway enrichment, functional interactome, The Cancer Genome Atlas (TCGA)-SCC data integration, and Western blot detection. In total, 1607 DEPs associated with cell adhesion and extracellular matrix proteins were identified in LSILs, whereas 1516 DEPs associated with catalytic and transport activities were identified in SCC; the proteins overexpressed in LSILs (332) were enriched in processes such as metabolism, immune response activation, and stress and cell death responses. In contrast, proteins overexpressed in SCC (205) were associated with the cell cycle, DNA damage, drug metabolism, proteasome degradation, methylation, and immune response. Interaction analyses highlighted proteins related to early proteins 1,5,6 and 7 (E1, E5, E6, and E7). In terms of the two DEPs, S100 calcium binding protein A10 (S100A10\/p11) and thymidine phosphorylase (TYMP) were detected in patients with LSIL, HSIL, and SCC at the protein level, consistent with their higher transcript levels in public datasets. Given the small, exploratory cohort, these findings are hypothesis-generating, and validation in a larger, balanced, independent cohort is required. In conclusion, this study identified DEPs associated with the progression of premalignant lesions to SCC that may represent candidate biomarkers and therapeutic targets warranting further investigation.<\/jats:p>","DOI":"10.3390\/pathogens15080793","type":"journal-article","created":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T16:11:56Z","timestamp":1785168716000},"page":"793","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Molecular Insights from Differential Proteomic Profiling of Premalignant Cervical Lesions and Cervical Cancer"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-0361-437X","authenticated-orcid":false,"given":"Diana Laura","family":"Gonzalez-Tolentino","sequence":"first","affiliation":[{"name":"Laboratorio de Biomedicina Molecular, Facultad de Ciencias Qu\u00edmico Biol\u00f3gicas, Universidad Aut\u00f3noma de Guerrero, Chilpancingo 39090, Guerrero, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0986-9453","authenticated-orcid":false,"given":"Olga Lilia","family":"Garibay-Cerdenares","sequence":"additional","affiliation":[{"name":"Laboratorio de Biomedicina Molecular, Facultad de Ciencias Qu\u00edmico Biol\u00f3gicas, Universidad Aut\u00f3noma de Guerrero, Chilpancingo 39090, Guerrero, Mexico"},{"name":"Secretaria de Ciencia, Humanidades, Tecnolog\u00eda e Innovaci\u00f3n, Investigadores por M\u00e9xico, Laboratorio de Biomedicina Molecular, Facultad de Ciencias Qu\u00edmico Biol\u00f3gicas, Universidad Aut\u00f3noma de Guerrero, Chilpancingo 39090, Guerrero, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7889-1681","authenticated-orcid":false,"given":"Sergio","family":"Encarnaci\u00f3n-Guevara","sequence":"additional","affiliation":[{"name":"Centro de Ciencias Gen\u00f3micas, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Cuernavaca 62210, Morelos, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c1ngel Gabriel","family":"Mart\u00ednez-Batallar","sequence":"additional","affiliation":[{"name":"Centro de Ciencias Gen\u00f3micas, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Cuernavaca 62210, Morelos, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-1449-1145","authenticated-orcid":false,"given":"Ramiro","family":"Alonso-Bastida","sequence":"additional","affiliation":[{"name":"Centro de Ciencias Gen\u00f3micas, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Cuernavaca 62210, Morelos, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3601-3893","authenticated-orcid":false,"given":"Jeovanis","family":"Gil","sequence":"additional","affiliation":[{"name":"Section for Clinical Chemistry, Department of Translational Medicine, Lund University, 22242 Lund, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5493-7905","authenticated-orcid":false,"given":"Jorge","family":"Organista-Nava","sequence":"additional","affiliation":[{"name":"Laboratorio de Biomedicina Molecular, Facultad de Ciencias Qu\u00edmico Biol\u00f3gicas, Universidad Aut\u00f3noma de Guerrero, Chilpancingo 39090, Guerrero, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2074-4889","authenticated-orcid":false,"given":"Luz del Carmen","family":"Alarc\u00f3n-Romero","sequence":"additional","affiliation":[{"name":"Laboratorio de Investigaci\u00f3n en Citopatolog\u00eda e Histoqu\u00edmica, Facultad de Ciencias Qu\u00edmico Biol\u00f3gicas, Universidad Aut\u00f3noma de Guerrero, Chilpancingo 39090, Guerrero, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3345-5859","authenticated-orcid":false,"given":"Marco 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