Explore the correlation between ARID1A and ANXA1 expressions in gastric cancer

抄録

Gastric cancer is leading cause of death worldwide. Although several therapeutic agents have been developed and showed positive efficacy for patients with gastric cancer, drug resistance remains severe problem during treatment. AT-rich interactive domain 1A (ARID1A) and annexin A1 (ANXA1) have a pivotal role in gastric tumorigenesis and reported as useful predictive or prognostic biomarkers. Previous study revealed that loss of ARID1A confers resistance to drugs that target the HER2/PI3K/mTOR pathway in breast cancer through activation of AKT via upregulation of ANXA1. Elevated ANXA1 levels are important for trastuzumab resistance and ANXA1 expression is inversely correlated with ARID1A levels in HER2-positive breast cancer. While trastuzumab is also used in HER2-positive gastric cancer, the expression status between ARID1A and ANXA1 in gastric cancer has yet to be determined. Here, we investigated both ARID1A and ANXA1 expressions by immunohistochemical staining in the test (n = 200) and validation (n = 220) cohorts of gastric cancer. Our results revealed that the inverse correlation between ARID1A and ANXA1 was not exist in patients with gastric cancer. The mRNA microarray analysis, which identified ARID1A-regulated genes in HER2-positive gastric cancer cells, revealed that ANXA1 was not induced by ARID1A knockdown. The present study suggested that the molecular relationship between ARID1A and ANXA1 is different in gastric cancer from in the breast cancer that ANXA1 serves as a predictive biomarker for trastuzumab-based treatment. Our results prompt a further study into the investigation of functional role of ARID1A and ANXA1 in gastric cancer.