ARID1A 阴性表达在胃癌中的预后作用。
Prognostic role of ARID1A negative expression in gastric cancer.
机构信息
Department of Gastrointestinal Tract Surgery, Fukushima Medical University School of Medicine, Fukushima, 960-1295, Japan.
Department of Cellular and Organ Pathology, Graduate School of Medicine, Akita University, Akita, 010-8543, Japan.
出版信息
Sci Rep. 2019 May 1;9(1):6769. doi: 10.1038/s41598-019-43293-5.
AT-rich interactive domain 1A (ARID1A) functions as a tumor suppressor and several therapeutic targets in ARID1A-mutated cancers are under development. Here, we investigated the prognostic value of ARID1A for gastric cancer and its association with expression of PD-L1 and p53. ARID1A expression was examined by immunohistochemistry and negative expression of ARID1A was detected in 39 (19.5%) of 200 cases in a test cohort and in 40 (18.2%) of 220 cases in a validation cohort. Negative expression of ARID1A was associated with worse overall survival in undifferentiated cases, particularly early-stage cases. Negative expression of ARID1A was detected in 11 (50%) of 22 PD-L1-positive cases and in 68 (17.1%) of 398 PD-L1-negative cases in a combined cohort. Negative expression of ARID1A was detected in 45 (22%) of 205 p53-positive cases and in 34 (15.8%) of 215 p53-negative cases in a combined cohort. In addition, expression of EZH2, a potential synthetic lethal target in ARID1A-mutated tumors, was detected in 79 ARID1A-negative cases. An ARID1A-knockdown gastric cancer cell line was subjected to microarray analysis, but no actionable targets or pathways were identified. The present results indicate that ARID1A may serve as an early-stage prognostic biomarker for undifferentiated gastric cancer.
富含 AT 的相互作用结构域 1A（ARID1A）作为肿瘤抑制因子发挥作用，目前正在开发针对 ARID1A 突变型癌症的几种治疗靶点。本研究旨在探讨 ARID1A 对胃癌的预后价值及其与 PD-L1 和 p53 表达的关系。采用免疫组织化学法检测 ARID1A 的表达，在一个检验队列的 200 例病例中，有 39 例（19.5%）和在一个验证队列的 220 例病例中，有 40 例（18.2%）检测到 ARID1A 表达阴性。在未分化型病例中，特别是早期病例，ARID1A 表达阴性与总生存期较差相关。在一个联合队列的 22 例 PD-L1 阳性病例中，有 11 例（50%）和在 398 例 PD-L1 阴性病例中，有 68 例（17.1%）检测到 ARID1A 表达阴性。在一个联合队列的 205 例 p53 阳性病例中，有 45 例（22%）和在 215 例 p53 阴性病例中，有 34 例（15.8%）检测到 ARID1A 表达阴性。此外，在 79 例 ARID1A 阴性病例中检测到 EZH2 的表达，EZH2 是 ARID1A 突变型肿瘤的潜在合成致死靶标。用 ARID1A 敲低的胃癌细胞系进行了微阵列分析，但未发现可行的靶点或通路。本研究结果表明，ARID1A 可能作为未分化型胃癌的早期预后生物标志物。
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