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Downregulation of CLCA4 expression is associated with the development and progression of colorectal cancer
Lihui Wei1,2, Wujin Chen3, Jinyan Zhao1,2
1Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, P.R. China.
Abstract:
The molecular mechanisms involved in the development and progression of colorectal cancer (CRC) are not completely understood. The present study aimed to identify potential novel genes involved in the development and progression of CRC. Database analysis revealed that the mRNA level of the chloride channel accessory 4 (CLCA4) was frequently lower in primary tumor tissues compared with that in corresponding non-cancerous colon tissues, and was even lower in liver metastases than in primary tumors. Further analyses through The Human Protein Atlas (THPA) website and immunohistochemistry (IHC)-based tissue microarray (TMA) confirmed that CLCA4 mRNA and protein expression were downregulated in CRC tissues. Furthermore, IHC-based TMA analysis revealed a gradual decrease in CLCA4 protein expression among colorectal normal, adenoma and carcinoma tissues. Survival analysis revealed that the decrease in CLCA4 mRNA expression was associated with the overall survival rate of patients with different types of tumor, including CRC, breast cancer, head and neck cancer and stomach cancer. Overall, downregulated CLCA4 expression may influence the development and progression of CRC.
Insights
Downregulated chloride channel accessory 4 (CLCA4) expression is linked to colorectal cancer progression. Lower CLCA4 levels in tumors and metastases suggest its role in cancer development and patient survival across multiple cancer types.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- The molecular underpinnings of colorectal cancer (CRC) development and progression remain incompletely elucidated.
- Identifying novel genes implicated in CRC pathogenesis is crucial for advancing therapeutic strategies.
Purpose of the Study:
- To investigate the role of chloride channel accessory 4 (CLCA4) in colorectal cancer.
- To identify CLCA4 as a potential novel gene involved in CRC development and progression.
Main Methods:
- Utilized database analysis to assess CLCA4 mRNA levels in tumor and non-cancerous tissues.
- Employed The Human Protein Atlas (THPA) and immunohistochemistry (IHC)-based tissue microarray (TMA) to confirm CLCA4 protein expression.
- Conducted survival analysis correlating CLCA4 expression with patient outcomes.
Main Results:
- CLCA4 mRNA levels were significantly lower in primary CRC tissues compared to adjacent normal tissues.
- CLCA4 expression was further reduced in liver metastases.
- Protein expression analysis confirmed CLCA4 downregulation in CRC tissues, with a progressive decrease from normal to adenoma to carcinoma.
- Decreased CLCA4 mRNA expression correlated with poorer overall survival in patients with CRC, breast cancer, head and neck cancer, and stomach cancer.
Conclusions:
- Downregulation of CLCA4 is a frequent event in colorectal cancer.
- Reduced CLCA4 expression may play a significant role in the development and progression of CRC.
- CLCA4 serves as a potential prognostic biomarker for patient survival across various cancer types.
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