{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T16:47:43Z","timestamp":1791478063021,"version":"4.3.4"},"reference-count":47,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,6,7]],"date-time":"2026-06-07T00:00:00Z","timestamp":1780790400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82160634"],"award-info":[{"award-number":["82160634"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"award":["82160634"],"award-info":[{"award-number":["82160634"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000865","name":"Bill and Melinda Gates Foundation","doi-asserted-by":"crossref","award":["72361127506"],"award-info":[{"award-number":["72361127506"]}],"id":[{"id":"10.13039\/100000865","id-type":"DOI","asserted-by":"crossref"}]},{"award":["72361127506"],"award-info":[{"award-number":["72361127506"]}],"id":[{"id":"https:\/\/ror.org\/0456r8d26","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007935","name":"Hainan Medical University","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100007935","id-type":"DOI","asserted-by":"crossref"}]},{"id":[{"id":"https:\/\/ror.org\/004eeze55","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Background: Esophageal squamous cell carcinoma (ESCA) represents one of the most common aggressive malignancies worldwide. Insulin-like growth factor binding protein 1 (IGFBP1), a typical member of the IGF superfamily, is closely linked to adverse prognosis in numerous cancers. Up to now, little is known about its functional relevance to cell migration and tumor progression in ESCA. This work focuses on clarifying the relationship between IGFBP1 expression and the progression and migratory characteristics of ESCA. Methods: mRNA expression profiles from ESCA patients were obtained from the TCGA and GEO databases. Differential expression analysis was performed using R software(version 4.2.2), followed by an intersection of DEGs between datasets. The STRING database was applied to establish PPI networks. Cytoscape software(Version 3.7.2) was then used for visual presentation and hub gene identification. IGFBP1 expression was validated in ESCA tissues versus adjacent normal tissues. Prognostic correlation was assessed using GEPIA, while diagnostic and predictive values were evaluated through ROC analysis and Cox regression. Genetic alterations of IGFBP1 were analyzed via cBioPortal. Immune cell infiltration patterns were investigated using TIMER. Functional enrichment analyses (GO, KEGG) were performed on IGFBP1-associated DEGs. In the in vitro experiments, esophageal cancer cell lines (such as Eca109 and TE-1) and normal human esophageal epithelial cell lines (such as HEEC) were selected. The transcriptional level of IGFBP1 was examined using RT-qPCR, while Western blot analysis was conducted to validate its protein expression changes. Changes in the proliferative capacity of cancer cells after IGFBP1 silencing were detected by the CCK-8 assay, and cell migration capacity was determined via wound scratch assays to clarify the related biological effects. Results: Overall, 2870 DEGs were screened from the GEO database, 153 DEGs were screened from the TCGA database, and 34 genes were found to be common to both databases; 10 core genes were screened from the PPI network. IGFBP1 was abnormally expressed in esophageal cancer. Cox regression confirmed that IGFBP1 is an independent risk factor, and prognostic analysis indicated that IGFBP1 is closely associated with poor prognosis. Gene mutation analysis showed that amplification mutations are the most common type of IGFBP1 gene mutation, and genetic alterations in IGFBP1 in ESCA patients are significantly associated with overall survival (OS) (p = 0.0002568). GO analysis indicated that IGFBP1-related differentially expressed genes were enriched in organic anion transport, epidermal development, apical cell components, and metal ion transmembrane transporter activity. Pathway enrichment based on the KEGG database illustrated the main enrichment of target genes in neuroactive ligand\u2013receptor interactions, calcium signaling and cAMP signaling pathways. Additionally, remarkable differences in immune cell infiltration were observed between IGFBP1 high-expression and low-expression subgroups through tumor immune profiling. IGFBP1 expression differed significantly between esophageal cancer cells and normal esophageal epithelial cells, as detected by RT-qPCR (p &lt; 0.05). Moreover, knockdown of IGFBP1 markedly inhibited the proliferation (p &lt; 0.05) and migration abilities (p &lt; 0.05) of TE-1 and Eca109 cells. Conversely, IGFBP1 overexpression facilitated these cellular processes. Conclusions: As a key oncogenic driver for ESCA, IGFBP1 may participate in the oncogenesis of ESCA, possibly influencing clinical outcomes via IGF signaling and the tumor microenvironment. Its dual functions in tumor and immune systems suggest it might be a candidate for ESCA immunotherapy research.<\/jats:p>","DOI":"10.3390\/genes17060668","type":"journal-article","created":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T07:43:02Z","timestamp":1780904582000},"page":"668","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["IGFBP1: A Key Regulatory Gene in the Oncogenesis and Progression of Esophageal Cancer"],"prefix":"10.3390","volume":"17","author":[{"given":"Jiaxin","family":"Zuo","sequence":"first","affiliation":[{"name":"Key Laboratory of Tropical Translational Medicine of Ministry of Education, School of Public Health, Hainan Medical University, Haikou 571199, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minmin","family":"Wen","sequence":"additional","affiliation":[{"name":"Key Laboratory of Tropical Translational Medicine of Ministry of Education, School of Public Health, Hainan Medical University, Haikou 571199, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiawen","family":"Li","sequence":"additional","affiliation":[{"name":"Key Laboratory of Tropical Translational Medicine of Ministry of Education, School of Public Health, Hainan Medical University, Haikou 571199, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Lv","sequence":"additional","affiliation":[{"name":"Key Laboratory of Tropical Translational Medicine of Ministry of Education, School of Public Health, Hainan Medical University, Haikou 571199, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yili","family":"Xuan","sequence":"additional","affiliation":[{"name":"Key Laboratory of Tropical Translational Medicine of Ministry of Education, School of Public Health, Hainan Medical University, Haikou 571199, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-1262-3261","authenticated-orcid":false,"given":"Xiwen","family":"Lu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Tropical Translational Medicine of Ministry of Education, School of Public Health, Hainan Medical University, Haikou 571199, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9961-2434","authenticated-orcid":false,"given":"Rongguang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Tropical Translational Medicine of Ministry of Education, School of Public Health, Hainan Medical University, Haikou 571199, China"},{"name":"Heinz Mehlhorn Academician Workstation, Hainan Medical University, Haikou 571199, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"110073","DOI":"10.1016\/j.compbiomed.2025.110073","article-title":"The role of oncostatin M in esophageal cancer and its potential as a prognostic maker","volume":"191","author":"Ding","year":"2025","journal-title":"Comput. 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