{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,8,15]],"date-time":"2025-08-15T00:42:57Z","timestamp":1755218577969,"version":"3.43.0"},"reference-count":37,"publisher":"IMR Press","issue":"7","license":[{"start":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T00:00:00Z","timestamp":1753833600000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Noncommunicable Chronic Diseases-National Science and Technology Major Project","award":["2024ZD0520200"],"award-info":[{"award-number":["2024ZD0520200"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["81802353"],"award-info":[{"award-number":["81802353"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Foundation of China Association for Promotion of Health Science and Technology","award":["JKHY2024003"],"award-info":[{"award-number":["JKHY2024003"]}]},{"name":"Science Foundation of Peking University Cancer Hospital","award":["A003004"],"award-info":[{"award-number":["A003004"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Front. Biosci. (Landmark Ed)"],"abstract":"<jats:p>Background: Efferocytosis (ER) plays a crucial role in the programmed clearance of dead cells, a process that is mediated by phagocytic immune cells. However, further exploration is needed to determine the full extent of its impact on the progression of pancreatic ductal adenocarcinoma (PDAC), particularly through interactions among tumor cells, stromal cells, and immune cells within the tumor microenvironment (TME). Methodology and Results: In this study, we comprehensively analyzed the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database, as well as additional databases from multiple bioinformatics websites, utilizing 167 ER features derived from the integration of single-cell RNA sequencing (scRNA-seq) and bulk transcriptomic data. A set of 14 ER-associated prognostic signatures, referred to as the \u201c14-gene panel\u201d genes, was identified based on overall survival (OS)\/disease-free survival (DFS) data, Pearson correlation coefficients, and multivariate Cox regression analyses. The model pathways enriched by the four-gene combination represented by \u201cLEAF\u201d and the 14-gene combination represented by the \u201c14-gene panel\u201d presented a high degree of similarity, including among the adhesion, mitotic, G2\/M checkpoint, and epithelial\u2012mesenchymal transition (EMT) signaling pathways. Least absolute shrinkage and selection operator (LASSO) regression was subsequently employed to construct an ER risk scoring system using deep learning, based on the following formula: LGALS3, EMP1, ASPH, and FNDC3B, collectively termed the \u201cLEAF\u201d panel. Additionally, random survival forest (RSF) algorithms facilitated the identification of a key panel of genes, designated \u201cLEAP\u201d genes, including LGALS3, EREG, ASPH, and PLS3; three of which genes (ASPH, LGALS3, and EREG) were identified as key factors influencing the behaviors of PDAC tumors, tumor-associated stroma, and macrophages. Finally, we utilized experimental methods, including Boyden chamber analyses, immunohistochemical staining, and cell cycle analyses, to demonstrate that interference with ASPH suppresses the malignant properties of tumors, including proliferation and migration. Multiplex immunofluorescence staining was employed to identify EREG as highly relevant to the M2 macrophage subpopulation. Conclusion: Our findings underscore the importance of considering a novel prognostic signature comprising 14 ER genes in the context of the TME when investigating the biology of PDAC. Future studies may explore how modulating these interactions could lead to novel therapeutic opportunities.<\/jats:p>","DOI":"10.31083\/fbl40818","type":"journal-article","created":{"date-parts":[[2025,8,6]],"date-time":"2025-08-06T06:16:39Z","timestamp":1754460999000},"source":"Crossref","is-referenced-by-count":0,"title":["A Novel 14-Gene Panel Associated With Efferocytosis for Predicting Pancreatic Cancer Prognosis Through Bulk and Single-Cell Databases"],"prefix":"10.31083","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-9611-1229","authenticated-orcid":true,"given":"Yaheng","family":"Wu","sequence":"first","affiliation":[{"name":"Department of Clinical Medicine, Beijing Luhe Hospital, Capital Medical University, 101149 Beijing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-6702-9550","authenticated-orcid":true,"given":"Lin","family":"Zhao","sequence":"first","affiliation":[{"name":"Key Laboratory of Carcinogenesis and Translational Research, Department of Thoracic Surgery II, Peking University Cancer Hospital & Institute, 100142 Beijing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dingyan","family":"Yi","sequence":"first","affiliation":[{"name":"College of Chemistry and Life Science, Beijing University of Technology, 100029 Beijing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-2923-9986","authenticated-orcid":true,"given":"Zhihua","family":"Tian","sequence":"first","affiliation":[{"name":"Key Laboratory of Carcinogenesis and Translational Research, Department of Central Laboratory, Peking University Cancer Hospital & Institute, 100142 Beijing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bin","family":"Dong","sequence":"first","affiliation":[{"name":"Key Laboratory of Carcinogenesis and Translational Research, Department of Central Laboratory, Peking University Cancer Hospital & Institute, 100142 Beijing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7015-3166","authenticated-orcid":true,"given":"Chunxiang","family":"Ye","sequence":"first","affiliation":[{"name":"Department of General Surgery, Beijing Chaoyang Hospital, Capital Medical University, 100020 Beijing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3340-5958","authenticated-orcid":true,"given":"Jingtao","family":"Liu","sequence":"first","affiliation":[{"name":"Key Laboratory of Carcinogenesis and Translational Research, Department of Pharmacology, Peking University Cancer Hospital & Institute, 100142 Beijing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-0257-5793","authenticated-orcid":true,"given":"Huachong","family":"Ma","sequence":"first","affiliation":[{"name":"Department of Acute Abdominal Surgery, Beijing Chaoyang Hospital, Capital Medical University, 100020 Beijing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6732-9466","authenticated-orcid":true,"given":"Wei","family":"Zhao","sequence":"first","affiliation":[{"name":"Key Laboratory of Carcinogenesis and Translational Research, Department of Clinical Laboratory, Peking University Cancer Hospital & Institute, 100142 Beijing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"16242","published-online":{"date-parts":[[2025,7,30]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","unstructured":"Wood LD, Canto MI, Jaffee EM, Simeone DM. 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Recent advances in research on aspartate \u03b2-hydroxylase (ASPH) in pancreatic cancer: A brief update. Bosnian Journal of Basic Medical Sciences. 2018; 18: 297\u2013304.","DOI":"10.17305\/bjbms.2018.3539"},{"key":"ref28","doi-asserted-by":"publisher","unstructured":"Ogawa K, Lin Q, Li L, Bai X, Chen X, Chen H, et al. Aspartate \u03b2-hydroxylase promotes pancreatic ductal adenocarcinoma metastasis through activation of SRC signaling pathway. Journal of Hematology & Oncology. 2019; 12: 144.","DOI":"10.1186\/s13045-019-0837-z"},{"key":"ref29","doi-asserted-by":"publisher","unstructured":"Lin Q, Chen X, Meng F, Ogawa K, Li M, Song R, et al. ASPH-notch Axis guided Exosomal delivery of Prometastatic Secretome renders breast Cancer multi-organ metastasis. Molecular Cancer. 2019; 18: 156.","DOI":"10.1186\/s12943-019-1077-0"},{"key":"ref30","doi-asserted-by":"publisher","unstructured":"Gan X, Li S, Wang Y, Du H, Hu Y, Xing X, et al. 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