Abstract
BackgroundThe aim of this study was to investigate the expression and prognostic significance of Uroplakin1A (UPK1A) in gastric adenocarcinoma patients. Functional studies were also analyzed in vitro.Methodology/Principal FindingsReal-time quantitative PCR (RT-qPCR), western blotting, and immunohistochemical (IHC) staining methods were used to analyze the expression of UPK1A in primary gastric adenocarcinoma tissue samples. Compared with matched adjacent non-tumor, the expression of UPK1A in fresh surgical specimens was reduced, which was confirmed by RT-qPCR (P<0.01) and western blotting analysis (P<0.01). The paraffin specimens from a consecutive series of 445 gastric adenocarcinoma patients who underwent surgery between 2003 and 2006 were analyzed by IHC staining. The relationship between UPK1A expression, clinicopathological factors, and survival were evaluated. IHC staining analysis revealed that the reduced expression of UPK1A was observed in 224 cases (50.3%). Additionally, the correlation analysis of clinicopathological factors demonstrated that reduced expression of UPK1A was significantly associated with histological grade (P = 0.022), node metastasis (P<0.001) and tumor node metastasis (TNM) stage (P = 0.008) (7th edition of the International Union Against Cancer (UICC)). Furthermore, Kaplan-Meier survival analysis revealed that the reduced expression of UPK1A was significantly associated with poor prognosis (P = 0.043). Cox hazards model analysis indicated that UPK1A expression was an independent risk factor at the 0.1 level (P = 0.094). The function of UPK1A in cell cycle, migration, and invasion was investigated by overexpressing UPK1A in the MKN45 gastric cancer cell line. The elevated expression of UPK1A cells induced G1 phase arrest and significantly inhibited migration and invasion.Conclusions/SignificanceThe reduced expression of UPK1A might play a role in the progression of gastric cancer. Thus, UPK1A could be a potential favorable biomarker associated with gastric cancer prognosis.
Highlights
Gastric carcinoma (GC) is the fourth most common cancer worldwide [1] and the second most frequent cause of cancerrelated deaths in China [2], with more new cases in China diagnosed every year than in any other country [3]
The positive UPK1A expression was localized to the cytoplasm, and reduced cytoplasmic UPK1A was observed in the tumor tissues, especially in the poorly differentially tumor tissues (Figure 3)
UPK1A belongs to the tetraspanin super family of genes that encode a large number of integral membrane proteins with four transmembrane domains (TMD) [7]
Summary
Gastric carcinoma (GC) is the fourth most common cancer worldwide [1] and the second most frequent cause of cancerrelated deaths in China [2], with more new cases in China diagnosed every year than in any other country [3]. Discovering and understanding the molecular and genetic characteristics of these tumorassociated genes would help us to improve the diagnosis and treatment of gastric cancer patients. If the molecular and genetic characteristics of gastric carcinoma could be better understood, the prognoses of patients may be improved and more appropriate therapies may be chosen. Uroplakins (UPs) play a central role in cellular physiology and cancer [4,5]. A study by Kar and colleagues [11] found that UPK1A can be used as a molecular biomarker and is a significant tumor suppressor in esophageal squamous cell carcinoma (ESCC), which demonstrated that UPK1A plays a role in inhibiting cell proliferation, clonogenicity, cell motility, and tumor formation. The aim of this study was to investigate the expression and prognostic significance of Uroplakin1A (UPK1A) in gastric adenocarcinoma patients.
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