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Transgelin as a suppressor is associated with poor prognosis in colorectal carcinoma patients
Liang Zhao1, Hui Wang, Yong-Jian Deng
1Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
Abstract:
We performed comparative proteomic analysis of colorectal cancer to investigate potential target proteins correlated with carcinogenesis and prognosis. Among them, transgelin, a 22 kDa protein also called SM22, was identified as a novel tumor suppressor protein, but little is known about this protein in tumors so far. A remarkable reduced expression of transgelin was found in colorectal cancer samples compared with normal colorectal mucosa. The effect of 5-aza-2'-deoxycytidine as a demethylation agent would obviously restore the original expression level of transgelin, implicating DNA hypermethylation of transgelin is important in the regulation of transgelin transcription in colorectal cancer. As a control, the investigation at cell line level confirms that transgelin protein comes from epithelium but not mesenchymal cells. Further, immunohistochemical staining for transgelin was performed on paraffin sections of 62 and 126 cases of normal colorectal mucosa and colorectal cancer specimens, respectively. As compared to normal colorectal tissue, we observed a significantly lower transgelin expression in colorectal cancer samples (P<0.001). Survival analysis demonstrated that patients without transgelin expression had shorter overall survival, whereas patients with transgelin expression had better survival (P=0.006). Multivariate analysis showed that negative transgelin expression was an independent prognostic indicator for patient's survival. Our results suggest that transgelin as a suppressor may serve as important biomarker of malignancy. Loss of transgelin involves gene promoter hypermethylation and is closely associated with poor overall survival in colorectal cancer patients.
Insights
Transgelin, a tumor suppressor, is significantly reduced in colorectal cancer due to DNA hypermethylation. Its loss correlates with poor prognosis, suggesting transgelin as a potential biomarker for malignancy.
Area of Science:
- Oncology
- Molecular Biology
- Proteomics
Background:
- Colorectal cancer (CRC) pathogenesis involves complex molecular alterations.
- Transgelin (SM22) is a protein with largely unknown roles in cancer.
- Reduced transgelin expression is observed in CRC, hinting at its potential tumor suppressor function.
Purpose of the Study:
- To investigate the role of transgelin in colorectal cancer.
- To determine the correlation between transgelin expression, carcinogenesis, and patient prognosis.
- To explore the regulatory mechanisms of transgelin expression in CRC.
Main Methods:
- Comparative proteomic analysis of colorectal cancer tissues.
- Demethylation studies using 5-aza-2'-deoxycytidine.
- Immunohistochemical staining of transgelin in normal and cancerous colorectal tissues (n=62 and n=126).
- Survival analysis and multivariate analysis.
Main Results:
- Transgelin expression was significantly reduced in colorectal cancer compared to normal mucosa (P<0.001).
- Demethylation treatment restored transgelin expression, indicating DNA hypermethylation's role.
- Loss of transgelin expression was associated with shorter overall survival (P=0.006) and identified as an independent prognostic indicator.
Conclusions:
- Transgelin acts as a tumor suppressor in colorectal cancer.
- Gene promoter hypermethylation contributes to transgelin downregulation in CRC.
- Transgelin expression serves as a potential biomarker for colorectal cancer malignancy and patient survival.
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