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TRIM28, a new molecular marker predicting metastasis and survival in early-stage non-small cell lung cancer
Lei Liu1, Enhong Zhao, Chunhui Li
1Department of Immunology, Basic Medical Institute, Chengde Medical College, Chengde, Hebei Province, 067000, China. homingreceptor@hotmail.com
Abstract:
TRIM28 is a universal corepressor for Kruppel-associated box zinc finger proteins. In this study, we demonstrated the expression of TRIM28 gene was significantly higher in cancerous tissues than in noncancerous tissues (P < 0.001). TRIM28 knockdown resulted in a decrease in cell proliferation in liquid media as well as in soft agar. The proliferation rate was impaired and the cell cycle progression was inhibited after knockdown of TRIM28 in non-small cell lung cancer cell lines PAa and SK-MES-1. We used real-time polymerase chain reaction to detect circulating cancer cells in 138 non-small cell lung cancer patients. The overall positive detection rate was 30.4% (42 of 138) in peripheral blood of NSCLC patients and was 29.9% (29 of 97) in early-stage patients. In a 70-month follow-up study, 20 of 29 patients (69.0%) in TRIM28 positive group had recurrence and/or metastasis, significantly higher (P = 0.004) than in the TRIM28 negative group (25 of 68, 36.8%). In addition, non-small cell lung cancer patients whose circulating cancer cells expressed TRIM28 suffered shorter tumor-specific survival compared with those with absent TRIM28 expression (P < 0.001). Results of our study showed that TRIM28 provides a survival advantage to lung cancer cells and may be a new marker to predict metastasis and prognosis in early-stage non-small cell lung cancer patients.
Insights
The TRIM28 gene is highly expressed in lung cancer, promoting cell growth and proliferation. TRIM28 detection in blood may predict metastasis and poor prognosis in non-small cell lung cancer patients.
Area of Science:
- Molecular Biology
- Oncology
- Gene Regulation
Background:
- Tripartite motif-containing protein 28 (TRIM28) functions as a corepressor for zinc finger proteins.
- Elevated TRIM28 expression is observed in various cancers, suggesting a role in tumorigenesis.
Purpose of the Study:
- To investigate the role of TRIM28 in non-small cell lung cancer (NSCLC) proliferation, metastasis, and patient prognosis.
- To evaluate TRIM28 as a potential biomarker for early-stage NSCLC.
Main Methods:
- TRIM28 gene expression analysis in cancerous versus noncancerous tissues.
- TRIM28 knockdown experiments in NSCLC cell lines (PAa and SK-MES-1) to assess proliferation and cell cycle.
- Real-time polymerase chain reaction (PCR) for detecting circulating tumor cells (CTCs) expressing TRIM28 in NSCLC patients.
- Longitudinal follow-up study to correlate TRIM28-positive CTCs with recurrence, metastasis, and survival.
Main Results:
- TRIM28 expression was significantly higher in NSCLC tissues compared to noncancerous tissues (P < 0.001).
- TRIM28 knockdown inhibited NSCLC cell proliferation and induced cell cycle arrest.
- TRIM28-positive CTCs were detected in 30.4% of NSCLC patients, including 29.9% of early-stage patients.
- TRIM28 positivity in CTCs significantly correlated with higher rates of recurrence/metastasis (69.0% vs 36.8%, P = 0.004) and shorter tumor-specific survival (P < 0.001).
Conclusions:
- TRIM28 significantly contributes to NSCLC cell survival and proliferation.
- Circulating TRIM28 expression serves as a potential predictive marker for metastasis and poor prognosis in early-stage NSCLC.
- TRIM28 represents a promising therapeutic target and diagnostic biomarker for NSCLC.
