Abstract:

Objective To investigate the role of phospholysine phosphohistidine inorganic pyrophosphate phosphatase （LHPP ） expression in patients with gastric adenocarcinoma and its effect on the biological function of carcinoma cells. Methods A total of 21 patients with gastric adenocarcinoma from the Affiliated Hospital of Jiangsu University from October 2020 to June 2021 were enrolled to collect gastric cancer tissues and adjacent tissues. The expression of LHPP in gastric cancer and its relationship with prognosis were analyzed by biological database. The expression of LHPP protein and mRNA in cancer tissues and adjacent tissues of patients with gastric cancer and different cell lines （human gastric mucosal epithelial cell line GES-1 and gastric cancer cell line HGC-27，AGS，MKN-45，SGC-7901，MGC-803） were determined. A gastric cancer cell interference model was constructed，and the effects of LHPP on the proliferation and migration of gastric cancer cells were evaluated by cell biology experiments. Gene Ontology （GO） enrichment and Kyoto Encyclopedia of Genes and Genomes（KEGG） signaling pathway analysis were used to evaluate the role of LHPP related genes. Results The analysis results of the Cancer Genome Atlas（TCGA），the Gene Expression Omnibus（GEO）and the Human Protein Atlas（HPA）databases showed that the LHPP mRNA and protein expressions in gastric cancer tissues were lower than those in adjacent tissues（P<0.05）. The analysis results of Kaplan-Meier Plotter database showed that the overall survival，first progression survival and reprogression survival of gastric cancer patients with high LHPP expression were longer than those with low LHPP expression [hazard ratios （HR） were 0.66，0.57 and 0.64，95% confidence intervals （CI） were 0.54-0.81，0.45-0.73 and 0.48-0.85，respectively]. The relative expression levels of LHPP protein and mRNA in all gastric cancer cell lines were statistically significant compared with GES-1 cells （P<0.05），and AGS cells were selected for follow-up tests. The relative expression levels of LHPP protein and mRNA in gastric cancer tissues were lower than those in adjacent tissues （P<0.05）. LHPP can inhibit the proliferation and migration of AGS cells. The main functions of LHPP in gastric cancer were cell cycle regulation in mitosis，positive regulation of DNA metabolism，protein folding，karyoplasmic transport and so on，mainly involved in cell cycle，TPX2 regulated AURKA activation，epigenetic regulation of gene expression and other signaling pathways. Conclusions The expression of LHPP is low in patients with gastric adenocarcinoma，which is related to the prognosis of patients，and LHPP has an inhibitory effect on the proliferation and migration of gastric adenocarcinoma cells.

Key words: Phospholysine phosphohistidine inorganic pyrophosphate phosphatase, Gastric carcinoma, Proliferation, Migration, Prognosis