2026-10-14T14:18:51Z https://api.figshare.com/v2/oai

oai:figshare.com:article/33922459 2026-09-18T07:17:09Z category_19 portal_316 item_type_3 month_year_09_2026

Table 1_The crotonylation reader DPF2 promotes the development and progression of colon adenocarcinoma through cell-type-specific immune regulation and metabolic reprogramming.xlsx Jingzhi Wang (2223439) Jingyi Zhou (3681790) Lin Liu (74495) Pharmacology colon adenocarcinoma crotonylation DPF2 metabolic reprogramming tumor immune microenvironment Background<p>The crotonylation reader DPF2 has been implicated in tumor progression, but its role in colon adenocarcinoma (COAD), especially in cell-type-specific immune regulation and metabolic reprogramming, remains unclear.</p>Methods<p>We conducted an integrative multi-omics study combining genetic association analysis for COAD, public transcriptomic validation data, CRC-context single-cell and spatial transcriptomic datasets used as supportive expression evidence, circulating metabolite profiling, and clinical immunohistochemistry. Two-sample Mendelian randomization was used to evaluate the association between genetically predicted expression of crotonylation-related genes and COAD risk, followed by validation and mechanistic analyses centered on DPF2.</p>Results<p>Among 16 crotonylation-related candidate genes with available cis-eQTL evidence, only DPF2 showed a significant positive association with COAD risk. DPF2 was consistently upregulated in GEO datasets, TCGA-COAD, and clinical samples, and high DPF2 expression was associated with advanced disease and poor overall survival. Single-cell MR identified the strongest risk-associated signal in TCL1A⁺ FCER2⁺ B cells, with a suggestive association in CD8⁺ S100B⁺ T cells. Supportive analyses using public CRC-context single-cell and spatial transcriptomic datasets further indicated heterogeneous immune-cell expression and tumor-region enrichment of DPF2. In addition, DPF2 was significantly associated with 11 COAD-related circulating metabolites, and mediation analyses suggested partial mediation through Ximenoylcarnitine (C26:1), 16α-hydroxy DHEA 3-sulfate, and Andro steroid monosulfate C19H28O6S (1).</p>Conclusion<p>DPF2 is a crotonylation reader associated with COAD risk and progression. Its effects may involve cell-type-specific immune regulation and partial mediation through metabolic reprogramming. While the primary causal inference of this study focused on COAD, complementary single-cell and spatial transcriptomic findings from broader CRC datasets provided supportive expression-level evidence consistent with these associations.</p> 2026-09-18T07:17:09Z Dataset Dataset 10.3389/fphar.2026.1835967.s001 https://figshare.com/articles/dataset/Table_1_The_crotonylation_reader_DPF2_promotes_the_development_and_progression_of_colon_adenocarcinoma_through_cell-type-specific_immune_regulation_and_metabolic_reprogramming_xlsx/33922459 CC BY 4.0