Reduced Expression of Uroplakin 1A Is Associated with the Poor Prognosis of Gastric Adenocarcinoma Patients

PLOS ONE, Dec 2019

Background The 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 Findings Real-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/Significance The 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.

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Reduced Expression of Uroplakin 1A Is Associated with the Poor Prognosis of Gastric Adenocarcinoma Patients

et al. (2014) Reduced Expression of Uroplakin 1A Is Associated with the Poor Prognosis of Gastric Adenocarcinoma Patients. PLoS ONE 9(4): e93073. doi:10.1371/journal.pone.0093073 Reduced Expression of Uroplakin 1A Is Associated with the Poor Prognosis of Gastric Adenocarcinoma Patients Yan Zheng 0 Dan-dan Wang 0 Wei Wang 0 Ke Pan 0 Chun-yu Huang 0 Yuan-fang Li 0 Qi- 0 Jing Wang 0 Shu-qiang Yuan 0 Shan-shan Jiang 0 Hai-bo Qiu 0 Yong-ming Chen 0 Xiao-fei Zhang 0 Bai-wei Zhao 0 Cong mai 0 Jian-chuan Xia 0 Zhi-wei Zhou 0 Rossella Rota, Ospedale Pediatrico Bambino Gesu', Italy 0 1 State Key Laboratory of Oncology in South China and Department of Experimental Research, Sun Yat-sen University Cancer Center , Guangzhou , People's Republic of China, 2 Department of Gastric and Pancreatic Surgery, Sun Yat-sen University Cancer Center , Guangzhou , People's Republic of China, 3 Research Center for Medicinal Biotechnology, Shandong Academy of Medical Sciences , Shandong , P.R. China , 4 Department of Endoscopy, Sun Yat-sen University Cancer Center , Guangzhou , People's Republic of China Background: The 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 Findings: Real-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/Significance: The 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. - Funding: This project supported by the National Natural Science Foundation of China (Grant No. 81172080 and 81201773) and the Specialized Research Fund for the Doctoral Program of Higher Education of China (Grant No. 20100171110084 and 20120171120114). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist. . These authors contributed equally to this work. 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]. Despite improvements in early diagnosis, advanced surgical techniques and combined therapy (surgery, chemotherapy and radiotherapy), distant metastasis and local recurrence cannot be avoided easily in most cases, and the prognosis of gastric cancer remains far from satisfactory [3]. The progression of gastric cancer is considered a multistep process that involves the activation of oncogenes and the inhibition of tumor suppressor genes. 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]. UPs are reportedly diminished and or absent in invasive carcinomas during tumorigenesis [6]. The Uroplakin 1A (UPK1A) gene belongs to the transmembrane 4 super family (TM4SF), also known as the tetraspanin family [7,8]. The express (...truncated)


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Yan Zheng, Dan-dan Wang, Wei Wang, Ke Pan, Chun-yu Huang, Yuan-fang Li, Qi-Jing Wang, Shu-qiang Yuan, Shan-shan Jiang, Hai-bo Qiu, Yong-ming Chen, Xiao-fei Zhang, Bai-wei Zhao, Cong mai, Jian-chuan Xia, Zhi-wei Zhou. Reduced Expression of Uroplakin 1A Is Associated with the Poor Prognosis of Gastric Adenocarcinoma Patients, PLOS ONE, 2014, Volume 9, Issue 4, DOI: 10.1371/journal.pone.0093073