Background and Aims: The family of coiled-coil domain-containing (CCDC) protein is of great biological significance, and its member CCDC34 is found to be overexpressed in various cancers and involved in tumor angiogenesis. However, its expression and function in gastrointestinal stromal tumors (GIST) have not been reported yet. This study was conducted to examine the CCDC34 expression and its relationship with angiogenesis in GIST. 
Methods: The CCDC34 expressions and the microvascular density (MVD) counts (labeled with CD34) in 84 specimens of GIST tissues and 30 specimens of normal gastrointestinal mucosal tissue were detected by immunohistochemical staining. The relationship between CCDC34 expression and clinicopathologic features of GIST patients as well as the MVD count were analyzed. Human GIST cells were transfected with CCDC34 overexpression vectors or CCDC34 interference vectors to establish CCDC34 overexpression and CCDC34 interference GIST882 cells through lentiviral transfection technique. Sixty nude mice were equally randomized into 3 groups, and were subcutaneously injected with untreated GIST882 cells (model group), CCDC34 overexpression GIST882 cells (overexpression group) and CCDC34 interference GIST882 cells (interference group) to create the tumor xenograft models. All nude mice were sacrificed 3 week later, the MVD counts and the protein expressions of PI3K, p-Akt, and VEGF-C in the tumor xenografts were determined by immunohistochemical staining and Western blot analysis, respectively. 
Results: The positive expression rate of CCDC34 in GIST tissue was significantly higher than that in normal gastrointestinal mucosal tissue (90.16% vs. 27.5%, χ2=10.295, P=0.001). The CCDC34 expression was irrelevant to the sex age and tumor site (all P>0.05), but was significantly related to tumor risk grade, tumor size, tumor cell mitotic and local invasion, necrosis and metastasis (all P<0.05); CCDC34 protein expression was positively correlated with MVD count (r=0.695, P<0.001). Compared with the model group, the MVD count and protein expressions of PI3K, p-Akt and VEGF-C in the xenograft tissues from overexpression group were significantly increased, while significant opposite changes in above parameters were observed in the xenograft tissues from interference group (all P<0.05).
Conclusion: The CCDC34 expression is increased in GIST, and CCDC34 overexpression can promote angiogenesis, and thereby enable GIST progression. The mechanism may be associated with activation of the PI3K/Akt signaling pathway. So, this pathway may become a new target for the treatment of GIST.