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We profiled the lysine lactylome of LSCC, paired it with adjacent normal tissues, and integrated the data with quantitative proteomic and transcriptomic analyses. LSCC exhibited a hyperlactate-associated phenotype characterized by dysregulated lactate-related genes (LRGs), altered protein abundance, increased tissue lactate, and globally increased Kla levels. Data-independent acquisition mass spectrometry (DIA-MS) identified 1616 Kla sites on 1468 peptides from 688 proteins, with most differential sites being upregulated in tumors. Differentially lactylated proteins were enriched in cell\u2013matrix adhesion, cell migration, chromatin remodeling, and gene-regulatory processes and were clustered into cytoskeletal and nuclear regulatory modules. Multiple Kla sites were also detected on the core histones. Immunoblotting and tissue microarray analyses confirmed increased pan-Kla expression in the LSCC. Pan-Kla levels were independent of sex and age but positively correlated with the tumor stage and lymph-node metastasis. These findings provide a systematic resource for hyperlactate-associated lactylome remodeling in LSCCs and identify candidate Kla-related molecular features associated with clinicopathological progression for future functional and clinical evaluation.<\/jats:p>","DOI":"10.1021\/acs.jproteome.5c01149","type":"journal-article","created":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T17:02:07Z","timestamp":1785949327000},"page":"4903-4918","source":"Crossref","is-referenced-by-count":0,"title":["Hyperlactate-Associated\nLysine Lactylome Remodeling\nin Laryngeal Squamous Cell Carcinoma"],"prefix":"10.1021","volume":"25","author":[{"given":"Dan","family":"Zhang","sequence":"first","affiliation":[{"name":"University of Electronic Science and Technology of China , , ,","place":["Chengdu, China, 610072"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinglan","family":"Li","sequence":"additional","affiliation":[{"name":"University of Electronic Science and Technology of China , , ,","place":["Chengdu, China, 610072"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huan","family":"Li","sequence":"additional","affiliation":[{"name":"University of Electronic Science and Technology of China , , ,","place":["Chengdu, China, 610072"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liang","family":"Wang","sequence":"additional","affiliation":[{"name":"University of Electronic Science and Technology of China , , ,","place":["Chengdu, China, 610072"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingze","family":"Li","sequence":"additional","affiliation":[{"name":"University of Electronic Science and Technology of China , , ,","place":["Chengdu, China, 610072"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Ran","sequence":"additional","affiliation":[{"name":"University of Electronic Science and Technology of China , , ,","place":["Chengdu, China, 610072"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Gong","sequence":"additional","affiliation":[{"name":"University of Electronic Science and Technology of China , , ,","place":["Chengdu, China, 610072"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaolong","family":"Zhao","sequence":"additional","affiliation":[{"name":"University of Electronic Science and Technology of China , , ,","place":["Chengdu, China, 610072"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-1598-5305","authenticated-orcid":true,"given":"Yu","family":"He","sequence":"additional","affiliation":[{"name":"University of Electronic Science and Technology of China , , ,","place":["Chengdu, China, 610072"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,8,5]]},"reference":[{"key":"2026090409134635000_cit1","doi-asserted-by":"publisher","DOI":"10.1016\/j.oraloncology.2025.107283","article-title":"Molecular\nfeatures of T and N stage progression in laryngeal cancer","volume":"165","author":"Li","year":"2025","journal-title":"Oral Oncol."},{"key":"2026090409134635000_cit2","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2025.1617613","article-title":"Global, regional,\nand national larynx cancer burden\nand health inequality analysis from 1990 to 2021 with a prediction\nfrom 2022 to 2040","volume":"15","author":"Jiang","year":"2025","journal-title":"Front Oncol."},{"issue":"3","key":"2026090409134635000_cit3","doi-asserted-by":"publisher","first-page":"229","DOI":"10.3322\/caac.21834","article-title":"Global cancer statistics\n2022: GLOBOCAN\nestimates of incidence and mortality worldwide for 36 cancers in 185\ncountries","volume":"74","author":"Bray","year":"2024","journal-title":"CA Cancer J. 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