Journal
ANNALS OF ONCOLOGY
Volume 25, Issue 7, Pages 1363-1372Publisher
OXFORD UNIV PRESS
DOI: 10.1093/annonc/mdu168
Keywords
gastric cancer; PAQR3; epithelial-mesenchymal transition (EMT); metastasis; prognosis
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Funding
- National Natural Science Foundation of China [81372332, 81130077, 81390350, 81321062]
- Natural Science Foundation of Zhejiang Province of China [LZ13H160002]
- Ministry of Science and Technology of China [2012CB524900]
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The aim of this study is to determine whether PAQR3, a protein specifically localized in the Golgi apparatus, is associated with tumor progression, metastasis and survival of human patients with gastric cancer. PAQR3 expression status was investigated in a large panel of gastric cancer (n = 300) and their corresponding para-cancerous histological normal tissues (PCHNT) at both mRNA and protein levels. The correlation of PAQR3 expression levels with clinical features such as metastasis and prognosis was analyzed. The effect of PAQR3 on the growth and migration of gastric cancer cells was also determined. PAQR3 was frequently down-regulated in gastric cancer samples compared with PCHNT at both mRNA and protein levels (both P < 0.0001). The expression level of PAQR3 was negatively correlated with Helicobacter pylori infection (P < 0.0001), tumor size (P < 0.0001), tumor stage (P < 0.0001), venous and lymphatic invasion (P < 0.0001), distant and nodal metastasis (P < 0.0001), and patient survival (P < 0.0001). Down-regulation of PAQR3 was highly correlated with increased epithelial-mesenchymal transition (EMT) in gastric cancer samples. In addition, PAQR3 overexpression was able to negatively modulate cell proliferation, migration and EMT of gastric cancer cells. PAQR3 is markedly down-regulated in human gastric cancers. PAQR3 expression level is closely associated with the progression and metastasis of gastric cancers. PAQR3 is also a new genetic signature that can predict the prognosis of the patients with gastric cancer.
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