1 3 J Cancer Res Clin Oncol DOI 10.1007/s00432-015-1964-8 ORIGINAL ARTICLE – CLINICAL ONCOLOGY Evaluation of the prognostic value and functional roles of CD44v6 in gastric cancer Jian-Wei Xie 1 · Peng-Chen Chen 2 · Chao-Hui Zheng 1 · Ping Li 1 · Jia-Bin Wang 1 · Jian-Xian Lin 1 · Jun Lu 1 · Qi-Yue Chen 1 · Long-Long Cao 1 · Mi Lin 1 · Yao Lin 2 · Chang-Ming Huang 1 Received: 31 January 2015 / Accepted: 16 March 2015 © Springer-Verlag Berlin Heidelberg 2015 classification and TNM stage. In MGC-803 cells, CD44 stimulated proliferation and colony formation, antagonized oxaliplatin-induced apoptosis, but did not affect migration. Conclusion CD44v6 is an important prognosis marker in gastric cancer. Tissue specificity may affect the functions of CD44v6, and further work is needed to elucidate its regulation. Keywords Gastric cancer · Cancer stem cell · CD44v6 · Therapeutic target Introduction Gastric cancer (GC) is the fourth most common malignancy and the third leading cause of cancer-related death world- wide (Correia et al. 2009; Lozano et al. 2012). Despite the decline in global patient number, GC remains one of the most prevalent cancers in China and over 40 % of new cases in the world are diagnosed in China (Ferro et al. 2014). Although the progress in early diagnosis and adju- vant therapy has improved the prognosis of GC patients, radical surgery is still the primary approach for GC treat- ment. More specific diagnostic and therapeutic targets are urgently needed for better clinical application in this field. Cancer stem cells (CSCs) in tumors are defined as a sub- population of tumor cells that have both tumor-initiating ability and the ability to reconstitute the cellular heteroge- neity typical of their tumors of origin (Schwitalla 2014). For tumors from epithelial origin including head and neck, breast, prostate and colon, isolation of CSCs is frequently based on their greater cell surface expression of CD44 (Al- Hajj et al. 2003; Collins et al. 2005; Dalerba et al. 2007; Li et al. 2007a). CD44 is a transmembrane glycoprotein participating in multiple cellular processes such as growth, Abstract Purpose Tumor stem cell surface marker CD44v6, a member of the CD44 protein family, is causally involved in the metastasis of cancer. Little is known about the functions of CD44v6 in gastric cancer. The aim of this study was to evaluate the prognostic value of CD44v6 and investigate its functional roles. Methods The expression of CD44v6 in 208 primary gas- tric adenocarcinoma patient samples was examined using immunohistochemistry and its correlation with clinico- pathological parameters, and 5-year patient survival was assessed. Two pairs of MGC-803 stable cells with either CD44v6 overexpression or knockdown were created. The effect of CD44v6 on cell proliferation, colony formation, migration and apoptosis was investigated using these two pairs of cells. Results Overexpression of CD44v6 was observed in all cancer cell lines. The 5-year survival rate of patients with positive CD44v6 expression is significantly worse com- pared to those with negative expression (38.8 vs. 73.6 %). CD44v6 and TNM stage are two independent prognostic factors of primary gastric adenocarcinoma. The risk fac- tors for the positive CD44v6 expression are location of tumor, depth of invasion, lymph node metastasis, Lauren * Yao Lin yaolin@fjnu.edu.cn; yaolinfjfz@gmail.com * Chang-Ming Huang hcmlr2002@163.com 1 Department of Gastric Surgery, Fujian Medical University Union Hospital, 29 Xinquan Road, Fuzhou 350001, Fujian Province, People’s Republic of China 2 College of Life Sciences, Fujian Normal University, Qishan Campus, Fuzhou 350108, Fujian Province, People’s Republic of China