Investigation of the relationship between ARID1A mutations and PI3K signaling pathway in gastric carcinomas

Gastric carcinoma represents a challenging malignancy due to its high mortality rates and heterogeneous molecular landscape. ARID1A, a tumor suppressor gene encoding a subunit of the SWI/SNF chromatin remodeling complex, is frequently mutated in gastric cancers. This study aimed to determine the ARID1A gene expression and mutation status in gastric carcinoma patients and to elucidate the relationship between these alterations and the PI3K/AKT/mTOR signaling pathway components (PI3KA, PI3KB, PTEN, AKT1, mTOR, PDK1, TSC1, FOXO1) as well as the immune checkpoint PD-L1. The study included 28 gastric carcinoma tissues and 9 non-tumor control tissues. Gene expression levels were analyzed using quantitative Real-Time PCR (qRT-PCR), and ARID1A genotype analysis was performed using the TaqMan Genotyping assay. Data were analyzed using the 2−ΔΔCt method. Our findings demonstrated a significant downregulation of ARID1A and PTEN mRNA levels in gastric carcinoma tissues compared to the control group (p<0,05), whereas PI3KA and PDK1 expressions were upregulated. Genotype analysis revealed that tumors harboring the ARID1A variant allele had significantly lower ARID1A mRNA expression compared to the wild-type. Furthermore, a strong correlation was detected between low ARID1A levels, high PD-L1 expression, and increased EZH2 levels. In conclusion, ARID1A loss is associated with PI3K/AKT pathway hyperactivation and immune evasion mechanisms, suggesting that this molecular signature could serve as a prognostic biomarker and a therapeutic target in gastric carcinoma.