PLOD1 promotes gastric cancer metastasis and immune escape by mediating extracellular matrix remodeling.

[BACKGROUND] Procollagen-lysine 2-oxoglutarate 5-dioxygenase 1 (PLOD1) is important for extracellular matrix formation and is involved in a variety of diseases, including cancer; however, its role in gastric cancer (GC) remains elusive. Therefore, this study aimed to explore the mechanistic importance of PLOD1 as a regulator of GC.

[METHODS] We examined the potential function and prognostic efficiency of PLOD1 in GC using a variety of bioinformatics methods. In vitro, we assessed the ability of PLOD1 to regulate GC by CCK-8 assay, Transwell assay, and Elisa assay analysis. Furthermore, we evaluated the effect of PLOD1 on the immune escape of GC cells by CCK-8 assay, flow cytometry, and Elisa assay.

[RESULTS] Analysis of PLOD1 expression in gastric cancer and other cancers in public databases as well as survival showed that low expression of PLOD1 has better survival, while the AUC area under the ROC curve of this gene showed that this gene has better prognostic value. Meanwhile, the results of correlation analysis between PLOD1 and 60 immune checkpoints showed that the gene was positively correlated with immune checkpoint genes, and one of the genes with the largest correlation was CD276, and the pearson's correlation between PLOD1 and cancer immune cycle was also calculated, and the relationship between PLOD1 and the immune microenvironment was evaluated, and the enrichment of the immune infiltration analysis into a larger number of immune cells among which the importance of PLOD1 was determined. Differential gene analysis was then performed on the gastric cancer dataset, using the differential genes to perform WGCNA network co-expression analysis with the PLOD1 gene, and then pathway enrichment analysis was performed on these differential genes, enriching for cancer-related pathways and cell cycle signaling pathways. Two key genes were then obtained in the analysis with glycolysis, while drug sensitivity analysis was performed, yielding multiple potential drugs such as AZD7545, BRD-K03911514 and BRD-K14844214. Furthermore, in vitro experiments further demonstrated that PLOD1 increased the proliferation and migration ability of GC cells by promoting immune escape.

[CONCLUSIONS] The results of this study suggest that PLOD1 is an important regulator of GC progression and participates in the immune escape process of GC, which is expected to be a potential target for GC treatment.