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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.

SUBMITTER: Xu JF

PROVIDER: S-EPMC5603835 | biostudies-other | 2017 Sep

REPOSITORIES: biostudies-other

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

Xu Jian-Feng JF Zhao Zhi-Guang ZG Ye Le-le LL Zhuge Weishan W Han Zheng Z Zhang Te-Ming TM Ye Si-Si SS Chen Wen-Jing WJ Zhu Shanli S Shi Li L Zhang Jun J Guo Ai-Zhen AZ Xue Xiang-Yang XY Shen Xian X

Cancer medicine 20170815 9

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 a ...[more]

PMID: 28812328

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Project description:Background: Lumican (LUM) is a member of the small leucine-rich proteoglycan family and plays dual roles as an oncogene and a tumor suppressor gene. The effect of LUM on tumors is still controversial. Methods: Gene expression profiles and clinical data of gastric cancer (GC) were downloaded from The Cancer Genome Atlas (TCGA) database. The expression difference of LUM in GC tissues and adjacent nontumor tissues was analyzed by R software and verified by quantitative real-time polymerase chain reaction (qRT-PCR) and comprehensive meta-analysis. The relationship between LUM expression and clinicopathological parameters was assessed by chi-square test and logistic regression. Kaplan-Meier survival analysis and Cox proportional hazards regression model were chosen to assess the effect of LUM expression on survival. Gene set enrichment analysis (GSEA) was used to screen the signaling pathways involved in GC between the low and the high LUM expression datasets. Results: The expression of LUM in GC tissues was significantly higher than that in adjacent nontumor tissues (P < 0.001) from the TCGA database. qRT-PCR (P = 0.022) and comprehensive meta-analysis (standard mean difference = 0.90, 95% CI: 0.34-1.46) demonstrated that LUM was upregulated in GC. The chi-square test showed that the high expression of LUM was correlated with tumor differentiation (P = 0.024) and T stage (P = 0.004). Logistic regression analysis showed that high LUM expression was significantly correlated with tumor differentiation (OR = 1.543 for poor vs. well or moderate, P = 0.043), pathological stage (OR = 3.149 for stage II vs. stage I, P = 0.001; OR = 2.505 for stage III vs. stage I, P = 0.007), and T classification (OR = 13.304 for T2 vs. T1, P = 0.014; OR = 18.434 for T3 vs. T1, P = 0.005; OR = 30.649 for T4 vs. T1, P = 0.001). The Kaplan-Meier curves suggested that patients with high LUM expression had a poor prognosis. Multivariate analysis showed that a high expression of LUM was an important independent predictor of poor overall survival (HR, 1.189; 95% CI, 1.011-1.400; P = 0.037). GSEA indicated that 14 signaling pathways were evidently enriched in samples with the high-LUM expression phenotype. Conclusions: LUM might act as an oncogene in the progression of GC and could be regarded as a potential prognostic indicator and therapeutic target for GC.

Dataset Information

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

Publications

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

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