Abstract
Tripartite motif-containing 24 (TRIM24), a member of the transcription intermediary factor 1 family, is defined as a co-regulator with several nuclear receptors, such as RARα. TRIM24 has been reported to be involved in many cancers. In this study, we aimed to investigate the expression pattern and prognostic significance of TRIM24 and its relationship with RARα in esophageal squamous cell cancer (ESCC). Both mRNA and protein expression levels of TRIM24 were found to be significantly decreased in ESCC, as judged by qRT-PCR and western blot. Immunohistochemistry staining shows that the reduced TRIM24 protein is associated with lymph node metastasis (P=0.024), advance pathological TNM (pTNM) stage (P=0.046) and recurrence/metastasis (P=0.001). Upregulated TRIM24 protein predicts longer overall survival and disease-free survival (both P<0.001) and is an independent predictor for good prognosis (HR, 0.519; 95%CI, 0.341-0.788; P=0.002). TRIM24 expression has been proven remarkably to improve prediction of survival of pTNM stage in ESCC patients, especially in stage I and II. However, no significant relationship was found between TRIM24 and RARα expression levels. In conclusion, reduced TRIM24 protein is associated with poor survival in ESCC patients, suggesting TRIM24 protein is a potential prognostic biomarker for ESCC.
Highlights
Esophageal cancer (EC) is one of the most common malignancies worldwide, with approximately 455,800 new cases and 400,200 deaths in 2012 [1]
The results demonstrate that the protein level of Tripartite motif‐containing 24 (TRIM24) in esophageal squamous cell cancer (ESCC) tissues is reduced in about 73.7% (14/19) of these ESCCs (P= 0.006, Fig. 1B and 1C), which is concordant with TRIM24 mRNA in ESCC
TRIM24, initially identified as a fusion partner of the Braf protein in the oncoprotein T18 found in mouse hepatocellular carcinoma [29], has been reported to be overexpressed in several kinds of cancers as aforementioned, which indicates that TRIM24 plays an oncogenic role in carcinogenesis
Summary
Esophageal cancer (EC) is one of the most common malignancies worldwide, with approximately 455,800 new cases and 400,200 deaths in 2012 [1]. In China, which is known as a high-incidence area, EC is one of the leading causes of cancer-related death [2], and most tumors (up to 90%) are esophageal squamous cell carcinomas (ESCC). Even in patients with curative treatment (resection with or without neoadjuvant therapy), the 5-year survival rate is only 35% – 45% [4]. A completely different prognosis and response to the same chemoradiotherapy (CRT) may be present in patients with the same TNM stage due to the large variability and heterogeneity of tumor cells. No molecular biomarker for ESCC is available in clinical routine practice. It is of great clinical value to identify new molecular biomarkers for improving www.aging‐us.com diagnosis, prognosis and response to CRT in the patients with esophageal cancer
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