Related Experiment Video
Updated: Aug 10, 2025
07:41
Performing Data Mining And Integrative Analysis Of Biomarker in Breast Cancer Using Multiple Publicly Accessible Databases
Published on: May 17, 2019
9.0K
Prognostic Significance of ARID1A Expression Patterns Varies with Molecular Subtype in Advanced Gastric Cancer
Jun Yong Kim1, Cheol Keun Park1, Songmi Noh2
1Department of Pathology, Yonsei University College of Medicine, Seoul, Korea.
Gut and Liver
|February 15, 2023
Summary
Loss of AT-rich interactive domain 1A (ARID1A) expression indicates a poorer prognosis in gastric cancer (GC) but only in cases that are MLH1-proficient and EBV-negative. This finding clarifies ARID1A's prognostic role in GC molecular subtypes.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- AT-rich interactive domain 1A (ARID1A) mutations are common in gastric cancer (GC), particularly in Epstein-Barr virus (EBV)-positive and microsatellite instability-high subtypes.
- Loss of ARID1A expression is often linked to a poor prognosis in GC, but its significance is complicated by its frequent alteration in favorable prognostic subtypes.
- This study aims to clarify the true prognostic value of ARID1A expression by accounting for confounding molecular factors.
Purpose of the Study:
- To investigate the prognostic significance of AT-rich interactive domain 1A (ARID1A) expression in a large cohort of advanced gastric cancer (GC) patients.
- To analyze the association between ARID1A expression patterns and key molecular features, including EBV-positivity and MLH1 deficiency.
- To determine the independent prognostic value of ARID1A expression in different GC molecular subtypes.
Main Methods:
- Evaluated ARID1A expression in 1,032 advanced GC cases using immunohistochemistry.
- Correlated ARID1A expression with clinicopathologic factors and molecular markers (EBV, MLH1 deficiency, p53, receptor tyrosine kinases).
- Performed survival analysis stratified by ARID1A expression and molecular subtypes (EBV status, MLH1 proficiency).
Main Results:
- Loss of ARID1A expression was significantly more frequent in MLH1-deficient (52.5%) and EBV-positive (35.8%) GCs compared to MLH1-proficient/EBV-negative GCs (9.6%).
- ARID1A loss was associated with worse prognosis exclusively in the MLH1-proficient and EBV-negative GC subgroup.
- Multivariate analysis confirmed that ARID1A loss and decreased expression are independent predictors of worse outcomes in advanced GC.
Conclusions:
- The prognostic impact of ARID1A loss in gastric cancer is context-dependent, specifically limited to MLH1-proficient and EBV-negative tumors.
- ARID1A expression serves as a crucial prognostic biomarker, but its interpretation requires consideration of EBV and MLH1 deficiency status.
- These findings refine the understanding of ARID1A's role in GC progression and patient outcomes.
