Related Experiment Video
Updated: Jan 16, 2026
Author Spotlight: Unveiling Transmembrane Protein Family-Related Markers in Gastric Cancer and Implications for Targeted Therapies
Published on: September 15, 2023
Integrated multi-omics analysis reveals PTM networks as key regulators of colorectal cancer progression and immune
Guiting Yang1,2,3,4,5, Liu Ji1,2,3,4, Chengmei Lv1,2,3,4,5
1Department of Anesthesiology, Guangxi Medical University Cancer Hospital, Nanning, China.
Background:
Colorectal cancer (CRC) is a leading cause of cancer mortality, with treatment resistance often driven by molecular heterogeneity and an immunosuppressive tumor microenvironment (TME). Post-translational modifications (PTMs) regulate key oncogenic processes, but their comprehensive role in CRC progression and immune evasion remains unexplored.
Methods:
We integrated multi-omics data from bulk RNA-seq (GEO/TCGA, n = 1,783), single-cell transcriptomics (41,143 cells), and Mendelian randomization. Differential expression, GSVA, and machine learning (LASSO/SVM/Random Forest) were used to identify PTM-associated signatures. Functional validation included spatial transcriptomics, and immune profiling.
Results:
Multi-omics analysis identified dysregulation in 80% of PTM pathways in CRC, with ubiquitination sustaining Wnt/β-catenin signaling and GALNT6-mediated glycosylation driving immune evasion through PD-L1 stabilization and CD8 + T cell exclusion. Single-cell analysis revealed GALNT6-specific enrichment in immune-excluded goblet cells (p < 0.05). Machine learning derived a 5-gene PTM Activity Signature (CCNB1IP1, GALNT6, NEDD4L, PSMD14, UBE2C) that distinguish between patients with diseases and those without (AUC = 1.00). GALNT6 was validated as a causal risk factor (OR = 1.10, 95%CI:1.01-1.18), with its inhibition synergizing with anti-PD-1 to enhance CD8 + T cell infiltration (p < 0.01).
Conclusion:
This study establishes PTM networks as central regulators of CRC progression and immune resistance. The PTM-AS framework enables precision subtyping, while GALNT6 emerges as a novel therapeutic target for overcoming immunotherapy resistance.
Insights
Post-translational modifications (PTMs) significantly impact colorectal cancer (CRC) progression and immune evasion. Targeting GALNT6, a key PTM enzyme, offers a novel strategy to enhance immunotherapy effectiveness in CRC patients.
Area of Science:
- Cancer Biology
- Immunology
- Molecular Biology
Background:
- Colorectal cancer (CRC) poses a significant mortality risk, often exacerbated by treatment resistance linked to molecular diversity and an immunosuppressive tumor microenvironment (TME).
- The role of post-translational modifications (PTMs) in CRC advancement and immune evasion remains incompletely understood.
Purpose of the Study:
- To comprehensively investigate the role of PTMs in colorectal cancer progression and immune evasion.
- To identify novel therapeutic targets for overcoming treatment resistance in CRC.
Main Methods:
- Integrated multi-omics data (bulk RNA-seq, single-cell transcriptomics) from 1,783 CRC patients.
- Applied differential expression analysis, Gene Set Variation Analysis (GSVA), and machine learning (LASSO, SVM, Random Forest) to identify PTM-associated signatures.
- Validated findings using spatial transcriptomics and immune profiling.
Main Results:
- Identified dysregulation in 80% of PTM pathways in CRC, with ubiquitination impacting Wnt/β-catenin signaling.
- GALNT6-mediated glycosylation was found to drive immune evasion via PD-L1 stabilization and CD8+ T cell exclusion.
- A 5-gene PTM Activity Signature (PTM-AS) accurately distinguished between disease and non-disease states (AUC=1.00).
- GALNT6 inhibition synergized with anti-PD-1 therapy to increase CD8+ T cell infiltration.
Conclusions:
- PTM networks are critical regulators of CRC progression and immune resistance.
- The PTM-AS framework facilitates precision subtyping of CRC.
- GALNT6 represents a promising therapeutic target for enhancing immunotherapy efficacy in colorectal cancer.
More Related Videos
08:42Establishment of a Co-culture System of Patient-Derived Colorectal Tumor Organoids and Tumor-Infiltrating Lymphocytes (TILs)
Published on: June 27, 2025
10:33Molecular Profiling of the Invasive Tumor Microenvironment in a 3-Dimensional Model of Colorectal Cancer Cells and Ex vivo Fibroblasts
Published on: April 29, 2014
Related Concept Videos
03:03mTOR Signaling and Cancer Progression
The mTOR pathway or the...
02:53Adaptive Mechanisms in Cancer Cells
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
02:17The Tumor Microenvironment
01:19Interactions Between Signaling Pathways
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...