Code and data for: Prognostic and Immune-Related Significance of DTL in Colorectal Cancer: an Integrative Multi-Omics Analysis

Background and Objectives Colorectal cancer (CRC) represents one of the most prevalent malignancies affecting the digestive system. The Denticleless E3 ubiquitin protein ligase homolog (DTL) plays a pivotal role in substrate recognition during the process of protein degradation. Nevertheless, its specific functions and underlying mechanisms in the context of CRC have yet to be elucidated. Repository Contents (What is in this upload) This repository contains the R scripts and processed data supporting the findings of the associated manuscript.- scripts/: R scripts for reproducing the figures (Figure1 to Figure6) in the paper.- data/: Processed datasets and differential expression results based on the intersection of GEO datasets GSE36400 and GSE10950, as well as TCGA data.- README.md: Detailed instructions on software requirements, installation, and execution order.- LICENSE: MIT License. Methods Datasets from GEO (GSE36400 and GSE10950, taking the intersection) and TCGA were used, and clinical specimens were collected from Zhongnan Hospital of Wuhan University. DTL expression was analyzed through databases, qRT-PCR, Western blot, and immunohistochemistry. Prognostic and clinicopathological correlations were evaluated using Cox regression and Kaplan-Meier analyses. Biological functions were assessed via GO/KEGG enrichment and various assays in CRC cell lines. Single-cell transcriptomics and immune profiling were conducted to study DTL in the tumor microenvironment and its link to immunotherapy response. Results DTL was overexpressed in CRC tissues and cell lines, linked to poorer survival (HR = 2.0897, 95% CI: 1.0155 - 7.268, p < 0.05), and identified as an independent prognostic risk factor. Reducing DTL inhibited CRC cell proliferation, invasion, and migration. Analysis of publicly available single-cell RNA sequencing data demonstrated enrichment of DTL in the T-proliferative subset, potentially indicating the proliferative state of these cells. Elevated DTL expression correlated with increased T-cell infiltration and macrophage polarization. Furthermore, computational analyses suggested a possible association between high DTL expression and a diminished response to cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) immunotherapy. Conclusion DTL is upregulated in CRC and associated with poor prognosis. It promotes proliferation, migration, and invasion in vitro. Its expression is associated with the tumor microenvironment and may be related to immunotherapy response, highlighting its potential as a prognostic and immune-related biomarker.