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This study applied proteomic profiling to investigate CPACs\u2019 inhibitory effects on reflux\u2010induced EAC in a rat model. Tandem mass spectrometry was applied to protein isolated from water\u2010, CPAC\u2010, and reflux\u2010exposed esophagi with and without CPAC treatment. Differentially expressed proteins were identified, followed by enrichment analyses to assess CPACs\u2019 capacity to ameliorate reflux\u2010induced changes in gene set hallmarks, pathways, and process networks. CPAC directly reversed 42.1% of reflux\u2010induced protein alterations. Gene set enrichment analysis (GSEA) revealed CPAC mitigated 11 hallmarks enriched in reflux\u2010induced EAC (i.e., oxidative phosphorylation, myogenesis, adipogenesis, MYC targets, and P53). Top pathways over\u2010represented with reflux and directly reversed by CPAC included spliceosome, metabolic pathways, and IL\u201017 signaling. Transcription_mRNA processing, translation_regulation\/initiation, and inflammation (i.e., kallikrein\u2010kinin system, neutrophil activation) dominated process networks upregulated by reflux and downregulated by CPAC. Networks exclusively altered by reflux and not mitigated by CPAC included ribosomal\u2010linked translation, immune response_antigen presentation, and leptin signaling. Similarly, CPAC did not reverse the reflux\u2010linked downregulation of ubiquinone metabolism. Identifying reflux\u2010induced cancer processes and pathways that CPAC fails to mitigate may inform opportunities for combination prevention efforts moving forward.<\/jats:p>","DOI":"10.1002\/mnfr.70102","type":"journal-article","created":{"date-parts":[[2025,5,24]],"date-time":"2025-05-24T15:43:49Z","timestamp":1748101429000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Proteomic Profiling Informs Mechanisms of Esophageal Adenocarcinoma Inhibition by Cranberry Proanthocyanidins"],"prefix":"10.1002","volume":"69","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9482-8276","authenticated-orcid":false,"given":"Yun","family":"Zhang","sequence":"first","affiliation":[{"name":"Surgery, Thoracic Surgery University of Michigan  Ann Arbor Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle","family":"Lee","sequence":"additional","affiliation":[{"name":"Surgery, Thoracic Surgery University of Michigan  Ann Arbor Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erika","family":"de Jesus","sequence":"additional","affiliation":[{"name":"Surgery, Thoracic Surgery University of Michigan  Ann Arbor Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine","family":"Weh","sequence":"additional","affiliation":[{"name":"Surgery, Thoracic Surgery University of Michigan  Ann Arbor Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Connor","family":"Howard","sequence":"additional","affiliation":[{"name":"Surgery, Thoracic Surgery University of Michigan  Ann Arbor Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henriette","family":"Remmer","sequence":"additional","affiliation":[{"name":"Surgery, Thoracic Surgery University of Michigan  Ann Arbor Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy B.","family":"Howell","sequence":"additional","affiliation":[{"name":"Surgery, Thoracic Surgery University of Michigan  Ann Arbor Michigan USA"},{"name":"Rutgers, The State University of New Jersey Marucci Center for Blueberry Cranberry Research"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4745-0522","authenticated-orcid":false,"given":"Laura A.","family":"Kresty","sequence":"additional","affiliation":[{"name":"Surgery, Thoracic Surgery University of Michigan  Ann Arbor Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,5,12]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/1759-7714.14745"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21871"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2022.05.054"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v19.i34.5598"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/ajg.2017.155"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0103508"},{"key":"e_1_2_9_8_1","doi-asserted-by":"crossref","unstructured":"S.Kambhampati A. 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