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Cancer Cell Int
2016 Oct 10;16:79. doi: 10.1186/s12935-016-0357-7.
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Expression of microtubule-associated protein TPX2 in human gastric carcinoma and its prognostic significance.
Shao C
,
Duan C
,
Wang J
,
Luan S
,
Gao Y
,
Jin D
,
Wang D
,
Li Y
,
Xu L
.
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BACKGROUND: The molecular mechanisms underlying the development and progression of gastric carcinoma remain poorly understood. The main objective of this study was to investigate the expression level of targeting protein for Xenopus kinesin-like protein 2 (TPX2) and its clinical significance in human gastric carcinoma.
METHODS: Real-time quantitative polymerase chain reaction (RT-PCR) and western blotting were used to determine the mRNA and protein levels of TPX2 in 20 paired gastric carcinoma tissues and the adjacent normal tissues, and the expression of TPX2 protein in 106 specimens of a gastric carcinoma tissue microarray was determined by immunohistochemistry. The associations of TPX2 expression with the clinicopathological features were analyzed, and the prognosis of gastric carcinoma patients was evaluated.
RESULTS: The results showed that the expression of TPX2 mRNA was significantly higher in gastric carcinoma than in the adjacent normal tissues in 20 paired samples. Western blotting analysis revealed that TPX2 protein was differentially increased in 17 of 20 specimens from primary human gastric carcinoma tissues compared with those from adjacent non-tumor tissues. Immunohistochemical staining showed that TPX2 over-expression was significantly associated with advanced age (P = 0.001) and tumor T stage (P = 0.003). In addition, TPX2 was an independent prognostic factor for overall survival (OS) in the multivariate analysis [hazard ratio (HR) 0.001; 95 % confidence interval (CI) 2.626-7.198; P = 0.001].
CONCLUSIONS: TPX2 is up-regulated in gastric carcinoma and is associated with old age and tumor T stage. TPX2 may serve as a good prognostic indicator in patients with gastric carcinoma.
Fig. 1.
TPX2 expression is up-regulated in human gastric carcinomas in the Oncomine database. Oncomine heat map of TPX2 gene expression in clinical gastric carcinoma samples compared with normal gastric tissues (http://www.oncomine.org). In the meta-analysis, TPX2 expression was significantly higher than that in the corresponding normal tissues in gastric carcinoma, with a median rank of 187.5 and a p value of 8.51Eâ8
Fig. 2. Overexpression of TPX2 mRNA in gastric carcinoma tissues. Expression levels of TPX2 mRNA in 20 paired gastric carcinoma tissues according to real-time PCR. The results show that the expression levels of TPX2 mRNA were significantly higher in tumor tissues than in the paired normal tissues (P = 0.002). Normal, matched adjacent non-tumor gastric tissues. Tumor, gastric carcinoma tissues. GAPDH was used as the internal control
Fig. 3. Overexpression of TPX2 protein in human gastric carcinoma tissues. a Western blot analyses of TPX2 protein expression in twenty matched pairs of gastric carcinoma (T) and adjacent noncancerous tissues (ANT). GAPDH was used as the loading control. b Immunohistochemical assay of TPX2 protein expression in six pairs of matched gastric carcinoma tissues. T gastric carcinoma tissues, ANT matched adjacent non-tumor gastric tissues (Ã400)
Fig. 4. Expression analysis of TPX2 protein by immunohistochemistry. TPX2 expression was mainly localized in the nucleus and cytoplasm of tumor cells. a Staining of TPX2 in normal gastric tissues (Ã400). b Low expression of TPX2 in gastric carcinoma tissues (stage II) (Ã400). c Medium expression of TPX2 in gastric carcinoma tissues (stage III) (Ã400). d Higher expression of TPX2 in gastric carcinoma tissues (stage IV) (Ã400)
Fig. 5. Correlation of TPX2 expression with patient overall survival in gastric carcinoma. KaplanâMeier curves with univariate analysis (log-rank). OS rates for cases with high TPX2 expression versus those with low TPX2 expression levels in all patients. High TPX2 expression was correlated with an unfavorable prognosis (P = 0.001)
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