ADAMTSL2 is an independent predictor for the prognosis of gastric cancer.

[AIMS] To explore novel biomarkers capable of predicting the prognosis of gastric cancer (GC) and investigate the mechanisms underlying the development of GC.

[METHODS] Firstly, differentially expressed genes (DEGs) in GC tumors and adjacent tissues were analyzed using transcriptome sequencing data. Then, the DEGs significantly associated with the prognosis of GC were selected. From this subset, genes with high protein expression levels in tumor tissues were focused. Multivariate hazard analysis was performed to further identify DEGs with independent prognostic value for GC patients. Eventually, the potential mechanisms involving DEGs that underlie the development of GC were investigated.

[RESULTS] Altogether, 25 previously DEGs that have not been reported before were discovered in the context of GC. Among these genes, ADAMTSL2, DSCC1, COL5A3, F2RL2, GRIN2D, IGSF6, IER5L, PLA2G7, PODNL1, RCN3 and RTN4RL2 were significantly associated with the overall survival, first progression and post progression survival of GC patients. Moreover, protein levels of ADAMTSL2, COL5A3, DSCC1, GRIN2D, PODNL1 and RCN3 were consistently highly expressed in clinical GC specimens. Furthermore, multivariate hazard analysis identified ADAMTSL2 as an independent predictor of GC prognosis. Further exploration revealed a potential regulatory connection between ADAMTSL2 and hsa-miR-7-2-3p. hsa-miR-7-2-3p was significantly down-regulated in GC and GC patients with low expression of hsa-miR-7 had a poor overall survival. Additionally, ADAMTSL2 was significantly co-expressed with key molecules (NOTCH1, NOTCH3, NOTCH4 and HEY1) in Notch signaling pathway.

[CONCLUSIONS] ADAMTSL2 stands out as an independent predictor for the prognosis of GC and may play a crucial pathological role in the development of GC.