{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T08:49:54Z","timestamp":1791622194457,"version":"4.3.4"},"reference-count":50,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T00:00:00Z","timestamp":1791590400000},"content-version":"vor","delay-in-days":282,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100005230","name":"Natural Science Foundation of Chongqing Municipality","doi-asserted-by":"publisher","award":["CSTB2024NSCQ-KJFZMSX0060"],"award-info":[{"award-number":["CSTB2024NSCQ-KJFZMSX0060"]}],"id":[{"id":"10.13039\/501100005230","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005230","name":"Natural Science Foundation of Chongqing Municipality","doi-asserted-by":"publisher","award":["CSTB2023NSCQ-LZX0052"],"award-info":[{"award-number":["CSTB2023NSCQ-LZX0052"]}],"id":[{"id":"10.13039\/501100005230","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["International Journal of Genomics"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>YTHDC1 is a nuclear N6\u2010methyladenosine reader involved in RNA processing. Its abundance, cellular distribution, and relationship with the immune microenvironment in hepatocellular carcinoma (HCC) remain incompletely characterized.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We integrated paired tumor\u2013adjacent transcriptomic and proteomic cohorts, three single\u2010cell RNA\u2010sequencing datasets containing 249,080 quality\u2010controlled cells, four outcome cohorts, three immune checkpoint inhibitor (ICI) cohorts, paired clinical specimens, and cell\u2010based YTHDC1\u2010knockdown assays. Patient\u2010level analyses covered hepatocyte programs, immune states, expression\u2010supported ligand\u2013receptor axes, survival, ICI response, and exploratory single\u2010cell network perturbation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      YTHDC1 protein abundance was higher in 160 paired CPTAC samples (Hedges\u2032\n                      <jats:italic>g<\/jats:italic>\n                      = 1.21, 95% confidence interval [CI] 1.01\u20131.42), whereas RNA effects varied across cohorts. Single\u2010cell analysis localized YTHDC1 across hepatic and immune compartments and identified patient\u2010level associations with hepatocyte, lymphoid, and myeloid programs. SPP1\u2013CD44 received the strongest cross\u2010cohort expression support among prespecified hepatocyte\u2010to\u2010myeloid axes. A transferred hepatocyte state showed a pooled tumor\u2013adjacent effect of\n                      <jats:italic>g<\/jats:italic>\n                      = 0.42 (95% CI 0.04\u20130.80), and higher YTHDC1 abundance was associated with poorer overall survival in study\u2010aware univariable models (hazard ratio 1.20, 95% CI 1.06\u20131.36). In 37 ICI\u2010treated patients, the pooled responder\u2013nonresponder effect for YTHDC1 was small (\n                      <jats:italic>g<\/jats:italic>\n                      = 0.05, 95% CI \u22120.60 to 0.71). Exploratory virtual knockout showed modest cross\u2010cohort agreement in network perturbation ranks. Paired clinical tissues supported increased YTHDC1 mRNA and protein abundance, and YTHDC1 silencing reduced proliferation\u2010related readouts and THP\u20101 migration in two HCC cell lines.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>YTHDC1 is increased at the protein level in HCC and is situated within identifiable hepatocyte and immune programs. Functional assays support its contribution to HCC cell proliferation and tumor cell\u2013dependent macrophage\u2010like cell migration under the tested conditions.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1155\/ijog\/6542992","type":"journal-article","created":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T08:34:07Z","timestamp":1791621247000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Cellular and Immune Context of YTHDC1 in Hepatocellular Carcinoma: A Single\u2010Cell and Multicohort Study"],"prefix":"10.1155","volume":"2026","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5068-3813","authenticated-orcid":false,"given":"Siqi","family":"Luo","sequence":"first","affiliation":[{"name":"Department of Hematology The Second Affiliated Hospital of Chongqing Medical University  Chongqing China  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