Abstract： Objective:To investigate the profile of PLXDC2 expression in gastric cancer tissues and the molecular mechanism by which PLXDC2 promotes the proliferation and clonal formation of gastric cancer cells.Methods:By retrieving the GEPIA and TCGA databases, the genes highly expressed in gastric cancer (tumor/normal>2) and significantly related to the clinical prognosis of gastric cancer were screened for overlap analysis. The target genes were determined by gene expression heatmap and the principle of high-expression-poor-prognosis. QRT-PCR and Western blotting were used to examine the expression of the target gene in 30 pairs of clinical gastric cancer tissue and normal adjacent tissue samples. After knock-down of target gene by transfection with interference siRNA, MTT cell proliferation assay, plate clone formation assay and flow cytometry were used to verify the effect of target genes on proliferation, clonal formation and cell cycle of gastric cancer. By retrieval and analysis of bioinformatics database for signal pathways involved in co-expression of the target gene, the potential molecular mechanism by which the target genes work in gastric cancer was explored and further determined.Results:The PLXDC2 mRNA (5.62±1.35) and protein (4.13±0.35) levels in gastric cancer tissues were significantly higher than those in cancer-adjacent normal tissues [mRNA (4.22±0.86) , protein (1.24±0.23) (both P<0.001) ]. With higher malignancy of gastric cancer, the PLXDC2 expression gradually increased, showing a clinical pattern of high-expression-poor-prognosis ( P<0.05) . On day 5 after culture with transfection, the proliferation rates of BGC-823 cells in the siPLXDC2#1 group (0.41±0.05) and siPLXDC2#2 group (0.35±0.07) were significantly lower than that in the siCTL group (0.58±0.08) ( P<0.01) . The rates of clonal formation in the siPLXDC2#1 group (0.49±0.07) and siPLXDC2#2 group (0.21±0.04) were significantly lower than that in the siCTL group (1.00±0.01) ( F=218.773, P<0.001) , and in these two groups, the cell cycle was significantly arrested at G1 phase. In the siPLXDC2#1 and siPLXDC2#2 groups, the levels of p-PI3K and P-AKT were significantly lower than those in the siCTL group ( P<0.001) , and the total expression of PI3K and AKT remained unchanged. Co-transfection with pcDNA3.1-PLXDC2 to the siPLXDC2 group of cells significantly reversed the inhibitory effects of siPLXDC2 on proliferation, clonal formation and signaling pathways of gastric cancer cells, and the cell level was shown to largely resume normal. Conclusion:The highly expressed PLXDC2 in gastric cancer may activate the PI3K/AKT signaling pathway, promote proliferation and clonal formation of gastric cancer cells, accelerate cell cycling, and participate in the development and progression of gastric cancer.