Prognostic significance of Daxx NCR (Nuclear/Cytoplasmic Ratio) in gastric cancer

Abstract

In addition to regulating apoptosis via its interaction with the death domain of Fas receptor, death domain associated protein 6 (Daxx) is also known to be involved in transcriptional regulation, suggesting that the function of Daxx depends on its subcellular localization. In this study, we aimed to explore Daxx subcellular localization in gastric cancer (GC) cells and correlate the findings with clinical data in GC patients. Seventy pairs of tissue samples (GC and adjacent normal tissue) were analyzed immunohistochemically for Daxx expression and localization (nuclear and cytoplasmic). The Daxx Nuclear/Cytoplasmic ratio (Daxx NCR) values in tissue microarray data with 522 tumor samples were further analyzed. The defined Prior cohort (n = 277, treatment between 2006 and 2009) and Recent cohort (n = 245, treatment between 2010 and 2011) were then used to examine the relationship between Daxx NCR and clinical data. The Daxx NCR was found to be clinically informative and significantly higher in GC tissue. Using Daxx NCR (risk ratio = 2.0), both the Prior and Recent cohorts were divided into high‐ and low‐risk groups. Relative to the low‐risk group, the high‐risk patients had a shorter disease free survival (DFS) and overall survival (OS) in both cohorts. Importantly, postoperative chemotherapy was found having differential effect on high‐ and low‐risk patients. Such chemotherapy brought no survival benefit, (and could potentially be detrimental,) to high‐risk patients after surgery. Daxx NCR could be used as a prognosis factor in GC patients, and may help select the appropriate population to benefit from chemotherapy after surgery.

Opposing biological functions of the cytoplasm and nucleus DAXX modified by SUMO-2/3 in gastric cancer

“…In further studies of primary and metastatic tissues, they revealed that DAXX expression was higher in various cancer metastases than in the corresponding primary tumors 24 . Our previous studies 16 also indicated that increased DAXX NCR was associated with poor clinical outcomes in patients with GC. However, little research has been carried out on the relationship between the subcellular localization of DAXX and the clinical features of GC.…”

“…Emerging evidence has suggested that DAXX is a key oncogene in tumorigenesis. Our previous study found that patients with GC often display a higher DAXX NCR 16 ; however, the underlying mechanisms of DAXX remains unknown. In this study, for the first time, we demonstrated that cDAXX and nDAXX expression have opposite effects on the survival prognosis of patients with GC.…”

CD2AP inhibits metastasis in gastric cancer by promoting cellular adhesion and cytoskeleton assembly

“…The study was approved by the Review Board of the Second Affiliated Hospital of Wenzhou Medical University. The tissue microarray (TMA) was constructed as described previously 20 . All the patients were aware of the research and signed the informed consent form.…”

“…Immunohistochemistry on a tissue microarray, constructed as described previously, 20 was performed for the detection of CD2AP expression. In brief, the sections were dewaxed by incubation with dimethyl benzene at 45°C for 60 minutes and then immersed in distilled water.…”

“…The tissue microarray (TMA) was constructed as described previously. 20 All the patients were aware of the research and signed the informed consent form.…”