Background and Aims: Gallbladder cancer is a malignant tumor originating from the biliary tract system, with insidious onset, high degree of malignancy and dismal prognosis. Golgi phosphorylation protein 3 (GOLPH3) is an oncogene that participates in the occurrence and development of tumors through initiating a series of signaling pathways. The expression profile and clinical significance of GOLPH3 in gallbladder cancer have not reported yet. Given that angiogenesis is an essential requirement for tumor growth, this study was conducted to investigate the expression of GOLPH3 in gallbladder cancer and its relations with the pro-angiogenic factor VEGF and tumor angiogenesis. 
Methods: Eighty specimens of gallbladder carcinoma tissue and 30 specimens of chronic cholecystitis tissue obtained from surgical resection in the 904th Hospital of Joint Logistic Support Force of PLA from January 2010 to December 2018 were collected. The expressions of GOLPH3 and VEGF and microvascular density (MVD) counts (distinguished by CD34 expression) in these specimens were determined by immunohistochemical staining. The relations of GOLPH3 and VEGF expressions and MVD count with the clinicopathologic factors and prognosis of the gallbladder cancer patients were analyzed, and the correlations among GOLPH3 and VEGF expressions and MVD count in gallbladder cancer tissue were also analyzed.
Results: Both positive expression rates of GOLPH3 and VEGF as well as the MVD count in gallbladder cancer tissue were significantly higher than those in chronic cholecystitis tissue (all P<0.05). The GOLPH3 expression and MVD count in gallbladder cancer tissue were significantly related to the degree of tumor differentiation, lymph node metastasis and the TNM stage of the patients (all P<0.05), and the VEGF expression in gallbladder cancer tissue was significantly related to the TNM stage and lymph node metastasis of the patients (all P<0.05). In gallbladder cancer tissue, there was a significant positive correlation between GOLPH3 expression and VEGF expression (r=0.437, P<0.05), and both their expression were positively correlated to the MVD count (r=0.416 and 0.433, both P<0.05). Survival analysis showed that the survival rate in patients with positive GOLPH3 or VEGF expression was significantly lower than that in respective negative ones (χ2=5.300 and 6.023, both P<0.05), while the survival rate of patients with high MVD count was significantly lower than that in those with low MVD count (χ2=11.986, P<0.05). 
Conclusion: The expression of GOLPH3 is closely associated with the malignant clinicopathologic features of gallbladder cancer and unfavorable outcomes of the gallbladder cancer patients. Based on the finding of pairwise correlations of GOLPH3 with VEGF and MVD, it is speculated that it facilitates the tumor angiogenesis by regulating the expression of VEGF, and thereby promote the growth and metastasis of gallbladder carcinoma.