{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T06:18:15Z","timestamp":1778221095033,"version":"3.51.4"},"reference-count":29,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T00:00:00Z","timestamp":1778198400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Hepatocellular carcinoma (HCC) exhibits profound molecular heterogeneity and aberrant cellular senescence. This study systematically dissects the senescence-associated molecular landscape to identify key regulators driving HCC progression and immune evasion.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Integrating multi-cohort transcriptomic datasets, we developed a robust prognostic signature using 101 machine-learning models, identifying prognostic signature. We employed preliminary proteomic, exploratory metabolomic, and single-cell RNA sequencing (scRNA-seq) analyses to explore multi-omics alterations. The functional senescence status and MCM7 were validated in a clinical HCC cohort by RT\u2013qPCR, Western blotting, immunohistochemistry, and multiplex immunofluorescence (mIF). Causality was established using\n                      <jats:italic>in vitro<\/jats:italic>\n                      functional assays in HepG2 cells.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A 12-gene random survival forest (RSF) signature accurately predicted patient survival across independent cohorts. MCM7 emerged as a central senescence-associated driver. ScRNA-seq and mIF confirmed MCM7 characterizes a highly proliferative, clonally expanding subset of CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cells within the tumor microenvironment.\n                      <jats:italic>In vitro<\/jats:italic>\n                      , MCM7 knockdown significantly inhibited HepG2 cell proliferation and upregulated senescence enforcers p16 and p21, whereas overexpression facilitated evasion. Additionally, TIDE analysis revealed that high-risk patients exhibited elevated immune evasion potential, predicting poor immunotherapy response.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This integrative multi-omics framework uncovers an MCM7 MCM7-driven senescence-associated axis promising HCC progression and immune dysfunction, offering a robust tool for prognostic stratification and novel therapeutic insights.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1762222","type":"journal-article","created":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T05:56:40Z","timestamp":1778219800000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Machine learning-driven multi-omics integration uncovers a senescence associated molecular axis in HCC"],"prefix":"10.3389","volume":"17","author":[{"given":"Talaiti","family":"Tuergan","sequence":"first","affiliation":[{"name":"Hepatobiliary and Echinococcosis Surgery Department, Digestive and Vascular Surgery Center, First Affiliated Hospital of Xinjiang Medical University","place":["Urumqi, China"]},{"name":"State Key Laboratory of Pathogenesis, Prevention and Management of High Incidence Diseases in Central Asia, Xinjiang Medical University","place":["Urumqi, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aimitaji","family":"Abulaiti","sequence":"additional","affiliation":[{"name":"Hepatobiliary and Echinococcosis Surgery Department, Digestive and Vascular Surgery Center, First Affiliated Hospital of Xinjiang Medical University","place":["Urumqi, China"]},{"name":"State Key Laboratory of Pathogenesis, Prevention and Management of High Incidence Diseases in Central Asia, Xinjiang Medical University","place":["Urumqi, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yierfan","family":"Yilihaer","sequence":"additional","affiliation":[{"name":"Hepatobiliary and Echinococcosis Surgery Department, Digestive and Vascular Surgery Center, First Affiliated Hospital of Xinjiang Medical University","place":["Urumqi, China"]},{"name":"State Key Laboratory of Pathogenesis, Prevention and Management of High Incidence Diseases in Central Asia, Xinjiang Medical University","place":["Urumqi, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bingwei","family":"Liu","sequence":"additional","affiliation":[{"name":"Hepatobiliary and Echinococcosis Surgery Department, Digestive and Vascular Surgery Center, First Affiliated Hospital of Xinjiang Medical University","place":["Urumqi, China"]},{"name":"State Key Laboratory of Pathogenesis, Prevention and Management of High Incidence Diseases in Central Asia, Xinjiang Medical University","place":["Urumqi, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yingmei","family":"Shao","sequence":"additional","affiliation":[{"name":"Hepatobiliary and Echinococcosis Surgery Department, Digestive and Vascular Surgery Center, First Affiliated Hospital of Xinjiang Medical University","place":["Urumqi, China"]},{"name":"State Key Laboratory of Pathogenesis, Prevention and Management of High Incidence Diseases in Central Asia, Xinjiang Medical University","place":["Urumqi, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tiemin","family":"Jiang","sequence":"additional","affiliation":[{"name":"Hepatobiliary and Echinococcosis Surgery Department, Digestive and Vascular Surgery Center, First Affiliated Hospital of Xinjiang Medical University","place":["Urumqi, China"]},{"name":"State Key Laboratory of Pathogenesis, Prevention and Management of High Incidence Diseases in Central Asia, Xinjiang Medical University","place":["Urumqi, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tuerganaili","family":"Aji","sequence":"additional","affiliation":[{"name":"Hepatobiliary and Echinococcosis Surgery Department, Digestive and Vascular Surgery Center, First Affiliated Hospital of Xinjiang Medical University","place":["Urumqi, China"]},{"name":"State Key Laboratory of Pathogenesis, Prevention and Management of High Incidence Diseases in Central Asia, Xinjiang Medical University","place":["Urumqi, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,5,8]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.3350\/cmh.2023.0070","article-title":"The latest global burden of liver cancer: a past and present threat","volume":"29","author":"Oh","year":"2023","journal-title":"Clin Mol Hepatol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jceh.2024.102446","article-title":"Global epidemiology of hepatocellular 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