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.
Highlights
Gastric cancer is a gastrointestinal malignancy with one of the poorest prognoses and is currently the malignancy with the second highest mortality rate in China [1]
There was no difference in nuclear mean optical density (MOD) when gastric cancer (GC) tissue was compared with adjacent normal tissue (P = 0.169) (Fig. 3C)
Image Pro Plus 6 was used to analyze the immuno-histochemical images for Daxx expression
Summary
Gastric cancer is a gastrointestinal malignancy with one of the poorest prognoses and is currently the malignancy with the second highest mortality rate in China [1]. The principal means of treatment is through surgical resection, which is widely considered as a radical form of treatment. Many patients with gastric cancer are diagnosed very late in their disease, thereby missing the optimal treatment time. Of those patients who undergo surgical resection, many eventually experience a recurrence of the cancer, with or without metastasis, after surgery; the 5-y ear overall survival rate is often less than 20% [2]. Accurate assessment of the prognosis, before and after treatment, is helpful in choosing the most appropriate treatment for patients with gastric carcinoma. An expansion of prognostic markers is urgently needed to reflect the complexity of neoplasia, as well as to provide a more accurate picture to guide our clinicians
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