Exploration of the ubiquitination-related molecular classification and signature to predict the survival and immune microenvironment in colon cancer

Ji-Zhong Xu¹, Tian-Qi Wan¹, Jin-Song Su¹

¹Department of Colorectal Surgery, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

Frontiers in Genetics

|September 13, 2024

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View abstract on PubMed

Summary

This study developed a colon cancer signature using ubiquitination-related genes (URGs) to predict prognosis and immune microenvironment. The signature identified high-risk patients with poor prognosis and immune escape, offering potential for improved colon cancer diagnosis and treatment.

Area of Science:

Oncology
Molecular Biology
Genetics

Background:

Ubiquitination is a key post-translational modification influencing cancer development and patient outcomes.
Colon cancer classification requires molecular-level understanding for improved treatment strategies.

Purpose of the Study:

To classify colon cancer using ubiquitination-related genes (URGs).
To develop a prognostic signature based on URGs for assessing the immune microenvironment and patient outcomes.
To identify potential diagnostic biomarkers for early colon cancer detection.

Main Methods:

Non-negative matrix factorization was used to subtype colon cancer based on URG expression.
ssGSEA and Estimate algorithms quantified immune cell infiltration and tumor microenvironment.
Lasso and SVM-RFE algorithms selected subtype feature genes.
A 6-gene URG signature was constructed and validated using Cox regression, ROC analysis, and external datasets.
Immune therapy response was assessed using TIDE, IPS, and submap analyses.
qRT-PCR, immunohistochemistry, and cell proliferation assays validated diagnostic and functional roles of specific URGs.

Main Results:

URGs stratified colon cancer patients into subtypes with distinct survival, immune infiltration, and pathological features.
A 6-gene signature (ARHGAP4, MID2, SIAH2, TRIM45, UBE2D2, WDR72) was identified.
High-risk patients showed increased epithelial-mesenchymal transition, immune escape, and immunosuppressive cells.
Low-risk patients responded better to CTLA4 checkpoint inhibitors.
ARHGAP4 and SIAH2 showed early diagnostic potential.
WDR72 knockdown inhibited colon cancer cell proliferation in vitro and in vivo.

Conclusions:

The developed URG signature and specific genes are promising biomarkers for colon cancer prognosis.
The signature aids in assessing the tumor immune microenvironment.
These findings support the use of URGs for colon cancer diagnosis and therapeutic target identification.

Keywords:

cell proliferation colon cancer immune microenvironment molecular classification prognosis ubiquitination

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