Comparative analysis of ARID1A mutations with mRNA levels and protein expression in gastric carcinoma.

ABSTRACT

The ARID1A gene is pivotal in chromatin remodeling and genomic integrity and is frequently mutated in various cancer types. ARID1A mutation is the second most frequently mutated tumor suppressor gene and has been suggested as a predictor of immunotherapeutic responsiveness in gastric carcinoma (GC). Despite its significance, the relationship among ARID1A somatic mutations, RNA expression levels, and protein expression remains unclear, particularly in GC. For this purpose, we performed comparative study in two cohorts. Cohort 1 used next-generation sequencing (NGS) to identify 112 GC cases with ARID1A mutations. These cases were compared with ARID1A immunohistochemistry (IHC) results. Cohort 2 employed microarray gene expression data to assess ARID1A RNA levels and compare them with ARID1A IHC results. In Cohort 1, 38.4% of ARID1A-mutated GC exhibited a complete loss of ARID1A protein when assessed by IHC, whereas the remaining 61.6% displayed intact ARID1A. Discordance between NGS and IHC results was not associated with specific mutation sites, variant classifications, or variant allele frequencies. In Cohort 2, 24.1% of the patients demonstrated a loss of ARID1A protein, and there was no significant difference in mRNA levels between the ARID1A protein-intact and -loss groups. Our study revealed a substantial discrepancy between ARID1A mutations detected using NGS and protein expression assessed using IHC in GC. Moreover, ARID1A mRNA expression levels did not correlate well with protein expression. These findings highlighted the complexity of ARID1A expression in GC.