{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T22:27:26Z","timestamp":1790029646035,"version":"4.0.1"},"reference-count":47,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2023,5,4]],"date-time":"2023-05-04T00:00:00Z","timestamp":1683158400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the General Research Funding","award":["17106921"],"award-info":[{"award-number":["17106921"]}]},{"name":"the General Research Funding","award":["17124219"],"award-info":[{"award-number":["17124219"]}]},{"name":"the General Research Funding","award":["T12-703\/19R"],"award-info":[{"award-number":["T12-703\/19R"]}]},{"name":"the General Research Funding","award":["C7026-18GF"],"award-info":[{"award-number":["C7026-18GF"]}]},{"name":"the General Research Funding","award":["C7021-21G"],"award-info":[{"award-number":["C7021-21G"]}]},{"name":"the General Research Funding","award":["82203794"],"award-info":[{"award-number":["82203794"]}]},{"name":"the General Research Funding","award":["82072757"],"award-info":[{"award-number":["82072757"]}]},{"name":"Theme-based Research Scheme","award":["17106921"],"award-info":[{"award-number":["17106921"]}]},{"name":"Theme-based Research Scheme","award":["17124219"],"award-info":[{"award-number":["17124219"]}]},{"name":"Theme-based Research Scheme","award":["T12-703\/19R"],"award-info":[{"award-number":["T12-703\/19R"]}]},{"name":"Theme-based Research Scheme","award":["C7026-18GF"],"award-info":[{"award-number":["C7026-18GF"]}]},{"name":"Theme-based Research Scheme","award":["C7021-21G"],"award-info":[{"award-number":["C7021-21G"]}]},{"name":"Theme-based Research Scheme","award":["82203794"],"award-info":[{"award-number":["82203794"]}]},{"name":"Theme-based Research Scheme","award":["82072757"],"award-info":[{"award-number":["82072757"]}]},{"name":"the Research Grant Council, Hong Kong","award":["17106921"],"award-info":[{"award-number":["17106921"]}]},{"name":"the Research Grant Council, Hong Kong","award":["17124219"],"award-info":[{"award-number":["17124219"]}]},{"name":"the Research Grant Council, Hong Kong","award":["T12-703\/19R"],"award-info":[{"award-number":["T12-703\/19R"]}]},{"name":"the Research Grant Council, Hong Kong","award":["C7026-18GF"],"award-info":[{"award-number":["C7026-18GF"]}]},{"name":"the Research Grant Council, Hong Kong","award":["C7021-21G"],"award-info":[{"award-number":["C7021-21G"]}]},{"name":"the Research Grant Council, Hong Kong","award":["82203794"],"award-info":[{"award-number":["82203794"]}]},{"name":"the Research Grant Council, Hong Kong","award":["82072757"],"award-info":[{"award-number":["82072757"]}]},{"name":"National Science Foundation of China (NSFC)","award":["17106921"],"award-info":[{"award-number":["17106921"]}]},{"name":"National Science Foundation of China (NSFC)","award":["17124219"],"award-info":[{"award-number":["17124219"]}]},{"name":"National Science Foundation of China (NSFC)","award":["T12-703\/19R"],"award-info":[{"award-number":["T12-703\/19R"]}]},{"name":"National Science Foundation of China (NSFC)","award":["C7026-18GF"],"award-info":[{"award-number":["C7026-18GF"]}]},{"name":"National Science Foundation of China (NSFC)","award":["C7021-21G"],"award-info":[{"award-number":["C7021-21G"]}]},{"name":"National Science Foundation of China (NSFC)","award":["82203794"],"award-info":[{"award-number":["82203794"]}]},{"name":"National Science Foundation of China (NSFC)","award":["82072757"],"award-info":[{"award-number":["82072757"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The application of steatotic liver graft has been increased significantly due to the severe donor shortage and prevalence of non-alcoholic fatty liver disease. However, steatotic donor livers are vulnerable to acute phase inflammatory injury, which may result in cancer recurrence. Alternative splicing events (ASEs) are critical for diverse transcriptional variants in hepatocellular carcinoma (HCC). Here, we aimed to depict the landscape of ASEs, as well as to identify the differential ASEs in steatotic liver graft and their association with tumor recurrence after transplantation. The overall portrait of intragraft transcripts and ASEs were elucidated through RNA sequencing with the liver graft biopsies from patients and rat transplant models. Various differential ASEs were identified in steatotic liver grafts. CYP2E1, ADH1A, CYP2C8, ADH1C, and HGD, as corresponding genes to the common pathways involved differential ASEs in human and rats, were significantly associated with HCC patients\u2019 survival. The differential ASEs related RNA-binding proteins (RBPs) were enriched in metabolic pathways. The altered immune cell distribution, particularly macrophages and neutrophils, were perturbated by differential ASEs. The cancer hallmarks were enriched in steatotic liver grafts and closely associated with differential ASEs. Our work identified the differential ASE network with metabolic RBPs, immune cell distribution, and cancer hallmarks in steatotic liver grafts. We verified the link between steatotic liver graft injury and tumor recurrence at post-transcriptional level, offered new evidence to explore metabolism and immune responses, and provided the potential prognostic and therapeutic markers for tumor recurrence.<\/jats:p>","DOI":"10.3390\/ijms24098216","type":"journal-article","created":{"date-parts":[[2023,5,4]],"date-time":"2023-05-04T02:28:02Z","timestamp":1683167282000},"page":"8216","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["The Landscape of Aberrant Alternative Splicing Events in Steatotic Liver Graft Post Transplantation via Transcriptome-Wide Analysis"],"prefix":"10.3390","volume":"24","author":[{"given":"Hui","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Surgery, School of Clinical Medicine, HKU-SZH & LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, China"},{"name":"Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of the Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yueqin","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Surgery, School of Clinical Medicine, HKU-SZH & LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9822-1335","authenticated-orcid":false,"given":"Kevin Tak-Pan","family":"Ng","sequence":"additional","affiliation":[{"name":"Department of Surgery, School of Clinical Medicine, HKU-SZH & LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chung-Mau","family":"Lo","sequence":"additional","affiliation":[{"name":"Department of Surgery, School of Clinical Medicine, HKU-SZH & LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kwan","family":"Man","sequence":"additional","affiliation":[{"name":"Department of Surgery, School of Clinical Medicine, HKU-SZH & LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,5,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"209","DOI":"10.3322\/caac.21660","article-title":"Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA Cancer J. 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