Low periostin expression predicts poor survival in intestinal type gastric cancer patients

Teming Zhang,1,* Zheng Han,1,* Arvine Chandoo,1,* Xincheng Huang,1 Xiangwei Sun,1 Lele Ye,2 Changyuan Hu,3 Xiangyang Xue,2 Yingpeng Huang,1 Xian Shen,1 Wenjun Chang,4 Xiaoming Lin5 1Department of General Surgery, Second Affiliated Hospital, Wenzhou Medical University, Wenzhou, People’s Republic of China; 2Department of Microbiology and Immunology, Institute of Molecular Virology and Immunology, Institute of Tropical Medicine, Wenzhou Medical University, Wenzhou, People’s Republic of China; 3Department of Gastrointestinal Surgery, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, People’s Republic of China; 4Department of Environmental Hygiene, Second Military Medical University, Shanghai People’s Republic of China; 5Department of Thoracic Surgery, The First Affiliated Hospital of Wenzhou Medical University, Nanbaixiang, Wenzhou, People’s Republic of China *These authors contributed equally to this work Background and aim: Periostin is a protein from the Fascilin family. It is commonly present in normal tissues and is responsible for cell adhesion. Evidence has emerged showing that changes in periostin expression play an important role in tumor initiation, development, and progression. This study aims to investigate the effect of periostin in gastric cancer (GC) patients who underwent gastrectomy. Seven hundred and forty-seven GC patients who underwent gastrectomy between December 2006 and July 2011 were included in this study. Methods: Seven hundred and forty-seven cancer tissues and 70 paired adjacent normal tissues were collected. Periostin expression was evaluated by immunohistochemistry. The Gene Expression Omnibus database was used to study the association between the mRNA level and patient’s overall survival. The tumor microenvironment was also studied. Results: Periostin expression in stroma was downregulated in tumor tissues but it was upregulated in the epithelial cells. After dividing the tissues according to the Lauren Classification, we found that periostin expression in stroma and epithelial cells was higher in intestinal type than in diffuse type (P<0.001 and P=0.010, respectively). Periostin was an independent predictor of lymph node (LN) metastasis in GC patients. The study of CD163(+) tumor-associated macrophages (TAMs) revealed that in diffuse type GC, periostin expression was associated with CD163(+) TAMs. Conclusion: We found that the periostin expression can predict LN metastasis in patients undergoing curative gastrectomy. Intestinal type GC patients with high periostin level had both a favorable survival and lesser LN metastasis. Keywords: lymph node metastasis, tumor microenvironment, tissue microarray, cell adhesion, Lauren Classificatio