4.6 Article

Loss of ARID1A expression is associated with systemic inflammation markers and has important prognostic significance in gastric cancer

Journal

JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY
Volume 148, Issue 7, Pages 1583-1595

Publisher

SPRINGER
DOI: 10.1007/s00432-022-03971-w

Keywords

Gastric cancer; ARID1A; Systemic inflammation markers; Immunotherapy; Nomogram

Categories

Funding

  1. National Natural Science Foundation of China [82073382]
  2. Distinguished Young Scholars of Jiangsu Province [BK20190001]

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This study explored the relationship between ARID1A expression and systemic inflammatory response (SIR), and investigated the prognostic value of ARID1A expression in gastric cancer (GC). The loss of ARID1A protein expression was associated with specific subtypes of GC and high expression of immune therapy markers. The expression of ARID1A protein had important prognostic significance in GC.
Background The tumor suppressor gene AT-rich interactive domain 1A (ARID1A) and systemic inflammatory response (SIR) have been reported to be related to the sensitivity to immunotherapy. This study intended to explore the relationship between ARID1A expression and SIR, and to further elucidate the prognostic value of ARID1A expression in gastric cancer (GC). Methods The mRNA and protein expression of ARID1A were detected in 272 formalin-fixed paraffin-embedded (FFPE) tumor tissues. The data of nine systemic inflammation markers were collected 1 week before gastrectomy. Univariate and multivariate COX analysis were used to screen out independent predictors of GC. Results Negative expression of ARID1A protein was related to GC with deficient mismatch repair (dMMR) (p = 0.033), positive programmed cell death-ligand 1 (PD-L1) (p = 0.005) and lower albumin level (p = 0.0064). Low expression of ARID1A mRNA was common in GC with abnormal E-cadherin (p = 0.020) and a higher platelet/lymphocyte ratio (PLR) (p = 0.0391). Multivariate COX analysis showed that the expression of ARID1A protein (p = 0.023), age (p = 0.004), T stage (p = 0.009) and N stage (p = 0.009) were independent predictors of GC. The nomogram established by independent predictors can accurately evaluate the survival risk of patients with GC. Conclusions The loss of ARID1A protein expression was associated with the dMMR subtype and high expression of PD-L1 in GC. Negative ARID1A protein and low expression of mRNA were associated with aberrant systemic inflammatory markers. The expression of ARID1A protein had important prognostic significance in GC.

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