Unique characteristics of ARID1A mutation and protein level in gastric and colorectal cancer: A meta-analysis

Abstract

Background/Aim: Recently, AT-rich interactive domain-containing 1A protein (ARID1A) has been identified as a novel tumor suppressor gene in gastric cancer (GC) and colorectal cancer (CRC). However, the clinicopathologic value of ARID1A mutation or protein level in GC and CRC patients is controversial. Hence, we conducted a meta-analysis on the relationship between ARID1A aberrations and clinicopathologic parameters in GC and CRC. Materials and Methods: Relevant published studies were selected from PubMed and EMBASE. The effect sizes of ARID1A mutation or level on the patient's clinicopathologic parameters were calculated by prevalence rate or odds ratio (OR) or hazard ratio (HR), respectively. The effect sizes were combined using a random-effects model. Results: The frequency of ARID1A mutation and loss of ARID1A protein expression in GC patients was 17% and 27%, respectively. The loss of ARID1A protein expression of GC patients was significantly associated with advanced tumor depth (OR = 1.8, P = 0.004), lymph node metastasis (OR = 1.4, P = 0.001), and unfavorable adjusted overall survival (HR = 1.5, P < 0.001). ARID1A mutation of GC was significantly associated with microsatellite instability (MSI) (OR = 24.5, P < 0.001) and EBV infection (OR = 2.6, P = 0.001). The frequency of ARID1A mutation and ARID1A protein expression loss in CRC patients was approximately 12-13%. Interestingly, the loss of ARID1A protein expression in CRC patients was significantly associated with poorly differentiated grade (OR = 4.0, P < 0.001) and advanced tumor depth (OR = 1.8, P = 0.012). Conclusion: Our meta-analysis revealed that ARID1A alterations may be involved in the carcinogenesis of GC by EBV infection and MSI. The loss of ARID1A protein expression may be a marker of poor prognosis in GC and CRC patients.