Authors

Xinian Wen*, Xiaoxia Ma**, Hongwei Zheng***, Chuanlian Chu***, Fang Zuo***, #

Departments

*Department of Gastrointestinal Surgery, Fifth Affiliated Hospital, Xinjiang Medical University, Urumqi, PR China - **Department of Endoscopy Center, Jinan Central Hospital, Jinan, PR China - ***Department of Gastroenterology, Jinan Central Hospital, Jinan, PR China

Abstract

Objective: To investigate the molecular mechanism of DOK3 involved in the development and progression of precancerous lesions and gastric cancer through PTK signaling pathway. 

Methods: Eighty-five patients with ESD and biopsy were enrolled in our hospital from January 2017 to May 2018. Immunohistochemistry was used to detect the expression of DOK3 in chronic superficial gastritis, low-grade intraepithelial neoplasia, advanced intraepithelial neoplasia and early gastric cancer. The siRNA of DOK3 was transfected into human gastric cancer MGC803 and BGC823 cells. Cell proliferation, invasion, migration and PTK2 expression were determined by CCK-8, cell scratch testing and RT-PCR, respectively. 

Results: The positive expression rates of DOK3 in chronic superficial gastritis, low-grade intraepithelial neoplasia, advanced intraepithelial neoplasia and early gastric cancer were 80.11 (20/25), 61.61% (9/15), 52.61% (7/15) and 37.61% (11/30), respectively. The positive expression of DOK3 in early gastric cancer tissues was significantly lower than that in chronic superficial gastritis, low-grade intraepithelial neoplasia and advanced intraepithelial neoplasia (P<0.05). The results of the CCK-8 method showed that, compared to the control group, OD value and proliferation capacity of the siDOK3-silenced group significantly increased after 24 h (P<0.05). The results of cell scratch testing demonstrated that, compared with the control group, the migration distance of cells in the siDOK3-silenced group was significantly prolonged, and the migration rate was significantly increased (P<0.05). Spearson analysis showed that there was a significant negative correlation between the expression of DOK3 and PTK2. Compared with the control group, PTK2 expression was significantly elevated in the siDOK3 transfection group (P<0.05). 

Conclusion: DOK3 has a low expression in early gastric cancer, and knocking out DOK3 can significantly promote the proliferation, invasion and migration of tumour cells, which may be involved in the occurrence and development of gastric cancer, is of great significance in the early stage of gastric cancer and is expected to be a new target for the diagnosis and treatment of gastric cancer.

Keywords

DOK3, PTK signaling pathway, precancerous lesions, gastric cancer

DOI:

10.19193/0393-6384_2020_3_199