Prognostic role of ARID1A negative expression in gastric cancer
Prognostic role of ARID1A negative expression in gastric cancer
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DOI：
10.1038/s41598-019-43293-5
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发表时间：
2019-05-01
影响因子：
4.6
通讯作者：
Kono, Koji
中科院分区：
文献类型：
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作者：
Ashizawa, Mai;Saito, Motonobu;Kono, Koji
富含 AT 的相互作用域 1A (ARID1A) 作为肿瘤抑制因子发挥作用，ARID1A 突变癌症的几个治疗靶点正在开发中。在这里，我们研究了 ARID1A 对胃癌的预后价值及其与 PD-L1 和 p53 表达的关系。通过免疫组织化学检查 ARID1A 表达，测试队列中 200 例病例中有 39 例（19.5%）检测到 ARID1A 阴性表达，验证队列中 220 例病例中有 40 例（18.2%）检测到 ARID1A 阴性表达。 ARID1A 的阴性表达与未分化病例（尤其是早期病例）的总生存率较差相关。在联合队列中，22 例 PD-L1 阳性病例中的 11 例（50%）和 398 例 PD-L1 阴性病例中的 68 例（17.1%）检测到 ARID1A 阴性表达。在联合队列中，205 例 p53 阳性病例中有 45 例（22%）检测到 ARID1A 阴性表达，215 例 p53 阴性病例中有 34 例（15.8%）检测到 ARID1A 阴性表达。此外，在 79 个 ARID1A 阴性病例中检测到 EZH2 的表达，EZH2 是 ARID1A 突变肿瘤中潜在的合成致死靶点。对 ARID1A 敲低的胃癌细胞系进行了微阵列分析，但没有发现可操作的靶点或途径。目前的结果表明 ARID1A 可以作为未分化胃癌的早期预后生物标志物。
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.