{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T15:12:54Z","timestamp":1778857974483,"version":"3.51.4"},"reference-count":43,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T00:00:00Z","timestamp":1773014400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82374531"],"award-info":[{"award-number":["82374531"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Shenzhen Science and Technology Program","award":["JCYJ20240813152313019"],"award-info":[{"award-number":["JCYJ20240813152313019"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Hepatocellular carcinoma (HCC) progression is shaped by crosstalk between the tumor immune microenvironment (TME) and metabolic reprogramming. This study aims to characterize a macrophage\u2013lactylation molecular axis in HCC and to develop a quantitative prognostic stratification model. Using the TCGA-LIHC cohort, differentially expressed genes were intersected with Paeoniflorin (PF)-related targets, HCC disease targets, and macrophage-\/lactylation-related genes to identify candidate genes. Prognostic genes were selected through Cox and LASSO-Cox analyses to construct a risk score model, followed by survival analysis and ROC curve evaluation. Immune infiltration was assessed using ESTIMATE and ssGSEA algorithms, and PF\u2013protein binding interactions were explored via molecular docking and molecular dynamics simulations. Intersection analysis identified eight key genes, and prognostic model genes (HNRNPU, LDHA, and NPM1) were used to construct the prognostic model. High-risk patients exhibited significantly poorer overall survival (p &lt; 0.001), with 1- and 3-year AUC values ranging from 0.70 to 0.90. HNRNPU was positively correlated with activated CD4 T cells (r = 0.385) and negatively correlated with eosinophils (r = \u22120.498). Molecular docking indicated favorable binding of PF to the model proteins, with the highest predicted affinity observed for LDHA (Vina score = \u22128.9 kcal\/mol), and molecular dynamics simulations suggested the formation of a stable LDHA\u2013PF complex during the later stage of the simulation. We propose a prognostic risk model for HCC constructed using three prognostic model genes and provide computational evidence linking PF to key molecular nodes such as LDHA. External cohort validation and experimental studies are warranted.<\/jats:p>","DOI":"10.3390\/ijms27052495","type":"journal-article","created":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T10:16:12Z","timestamp":1773051372000},"page":"2495","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Bioinformatics Profiling of a Paeoniflorin-Associated \u201cMacrophage\u2013Lactylation\u201d Axis in Hepatocellular Carcinoma: An LDHA-Based Prognostic Model and Structural Computational Evidence"],"prefix":"10.3390","volume":"27","author":[{"given":"Kongli","family":"Fan","sequence":"first","affiliation":[{"name":"The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen 518033, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruiqi","family":"Zhao","sequence":"additional","affiliation":[{"name":"The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen 518033, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jialing","family":"Sun","sequence":"additional","affiliation":[{"name":"The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen 518033, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"Li","sequence":"additional","affiliation":[{"name":"The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen 518033, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Minling","family":"Lv","sequence":"additional","affiliation":[{"name":"The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen 518033, China"},{"name":"Faculty of Chinese Medicine, Macau University of Science and Technology, Macao 999078, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mengqing","family":"Ma","sequence":"additional","affiliation":[{"name":"The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen 518033, China"},{"name":"Faculty of Chinese Medicine, Macau University of Science and Technology, Macao 999078, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiesheng","family":"Guo","sequence":"additional","affiliation":[{"name":"The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen 518033, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4758-0060","authenticated-orcid":false,"given":"Xiaozhou","family":"Zhou","sequence":"additional","affiliation":[{"name":"The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen 518033, China"},{"name":"Faculty of Chinese Medicine, Macau University of Science and Technology, Macao 999078, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1016\/j.ccell.2024.01.007","article-title":"Precision treatment in advanced hepatocellular carcinoma","volume":"42","author":"Yang","year":"2024","journal-title":"Cancer Cell"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"100815","DOI":"10.1016\/j.bj.2024.100815","article-title":"Hepatocellular carcinoma systemic treatment update: From early to advanced stage","volume":"48","author":"Teng","year":"2025","journal-title":"Biomed. 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