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Integrated transcriptomics and proteomics data analysis identifies CDH17 as a key cell surface target in colorectal
1Department of Immunology, School of Medical Sciences, Universiti Sains Malaysia, 16150 Kelantan, Malaysia.
Computational Biology and Chemistry
|May 29, 2023
Summary
Identifying new immunotherapy targets for colorectal cancer (CRC) is crucial. This study identified cadherin 17 (CDH17) as a promising cell surface target for CRC therapy due to its high expression in tumors and restricted normal tissue presence.
Area of Science:
- Oncology
- Immunotherapy
- Bioinformatics
Background:
- Developing effective immunotherapies for colorectal cancer (CRC) is challenging due to the absence of suitable cell surface targets.
- Ideal targets should be highly expressed on cancer cells while minimally present in normal tissues to prevent off-tumor toxicities.
Purpose of the Study:
- To identify and rank potential cell surface targets for immunotherapy in colorectal cancer (CRC).
- To evaluate gene expression profiles in CRC and normal tissues to find targets with restricted expression.
Main Methods:
- In silico analysis of 13,488 genes from the Human Protein Atlas (HPA) database for CRC.
- Shortlisting targets based on absence in brain/lung, restricted normal tissue expression, cell surface localization, and moderate CRC expression.
- Ranking shortlisted targets using transcript and protein expression data from multiple CRC datasets (DepMap, TCGA, CPTAC-2, HPA).
Main Results:
- Fifteen potential cell surface targets were shortlisted.
- Cadherin 17 (CDH17) emerged as the top-ranked target with high and homogeneous expression in CRC.
- CDH17 expression correlated with carcinoembryonic antigen and was inversely associated with microsatellite instability and immune markers in CRC.
Conclusions:
- Cadherin 17 (CDH17) is a highly promising cell surface target for therapeutic development in colorectal cancer (CRC).
- The study presents a novel computational framework for identifying cell surface targets applicable to other malignancies.
- Targeting CDH17 may offer a strategy to improve immunotherapy efficacy and reduce toxicity in CRC treatment.
