Lactylation-based gene signature and gastric adenocarcinoma

Gastric adenocarcinoma (STAD) is a type of stomach cancer that accounts for 95% of gastric cancers and has poor survival rates. A recent study focused on a biological process called "lactylation," where lactate molecules attach to proteins, influencing metabolism and gene expression in cancer. The study aimed to identify lactylation-related genes (LRGs) that could predict patient outcomes and immune system involvement in STAD.

Researchers analyzed data from 375 STAD samples and 32 normal tissues, identifying 12 key LRGs. They built a six-gene model (including DHRS7, NOP2, CRABP2, CALD1, ALB, and RIMS1) to predict patient survival. Patients with higher risk scores had shorter survival times. Among these genes, DHRS7 was studied in-depth.

DHRS7 levels were lower in cancer tissues but higher in advanced stages, correlating with worse outcomes. It was linked to immune cells like macrophages, particularly M2 macrophages, which promote an immunosuppressive tumor environment. DHRS7 also influenced key cancer pathways (e.g., PI3K-AKT and TGF-β) and processes like tumor growth, invasion, and immune escape.

Interestingly, DHRS7 acted as a tumor suppressor in early stages but promoted cancer in later stages, similar to other proteins like TGF-β. This dual role makes it a potential target for personalized therapies. The study suggests that lactylation-based gene signatures, especially DHRS7, could serve as biomarkers for prognosis and guide immunotherapy or metabolism-focused treatments in STAD. However, further research is needed to validate these findings and explore DHRS7's mechanisms.