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Updated: Jul 10, 2025
Genome-Wide Analysis of DNA Methylation in Gastrointestinal Cancer
Published on: September 18, 2020
Data Mining Suggests That CXCL14 Gene Silencing in Colon Cancer Is Due to Promoter Methylation
Yanjing Wang1, Siyi Wang1, Yuchen Niu1
1Engineering Research Center of Cell & Therapeutic Antibody, School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China.
Abstract:
CXCL14 is one of the most evolutionarily conserved members of the chemokine family and is constitutionally expressed in multiple organs, suggesting that it is involved in the homeostasis maintenance of the system. CXCL14 is highly expressed in colon epithelial cells and shows obvious gene silencing in clinical colon cancer samples, suggesting that its silencing is related to the immune escape of cancer cells. In this paper, we analyzed the expression profiles of multiple human clinical colon cancer datasets and mouse colon cancer models to reveal the variation trend of CXCL14 expression during colitis, colon polyps, primary colon cancer, and liver metastases. The relationship between CXCL14 gene silencing and promoter hypermethylation was revealed through the colorectal carcinoma methylation database. The results suggest that CXCL14 is a tumor suppressor gene in colorectal carcinoma which is activated first and then silenced during the process of tumor occurrence and deterioration. Promoter hypermethylation is the main cause of CXCL14 silencing. The methylation level of CXCL14 is correlated with the anatomic site of tumor occurrence, positively correlated with patient age, and associated with prognosis. Reversing the hypermethylation of CXCL14 may be an epigenetic therapy for colon cancer.
Insights
Chemokine CXCL14, a tumor suppressor, is silenced in colon cancer due to promoter hypermethylation. Reversing this epigenetic change may offer a new colon cancer therapy.
Area of Science:
- Oncology
- Molecular Biology
- Epigenetics
Background:
- Chemokine CXCL14 is evolutionarily conserved and crucial for maintaining system homeostasis.
- CXCL14 is highly expressed in colon epithelial cells but silenced in clinical colon cancer, suggesting a role in immune evasion.
Purpose of the Study:
- To analyze CXCL14 expression trends during colorectal carcinoma progression.
- To investigate the link between CXCL14 gene silencing and promoter hypermethylation.
- To explore CXCL14's role as a tumor suppressor in colorectal carcinoma.
Main Methods:
- Analysis of human clinical colon cancer datasets and mouse colon cancer models.
- Examination of CXCL14 expression variations across disease stages (colitis, polyps, primary cancer, metastasis).
- Utilized colorectal carcinoma methylation database to assess gene silencing mechanisms.
Main Results:
- CXCL14 expression decreases during the progression from colitis to liver metastases.
- Promoter hypermethylation is identified as the primary cause of CXCL14 gene silencing.
- CXCL14 methylation levels correlate with tumor location, patient age, and prognosis.
Conclusions:
- CXCL14 functions as a tumor suppressor gene in colorectal carcinoma, initially activated then silenced.
- Promoter hypermethylation is the key mechanism driving CXCL14 silencing.
- Targeting CXCL14 hypermethylation presents a potential epigenetic therapy strategy for colon cancer.
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