ANO9 调节胃癌中 PD-L2 的表达和与 PD-1 的结合能力。
ANO9 regulates PD-L2 expression and binding ability to PD-1 in gastric cancer.
机构信息
Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Department of Pathology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
出版信息
Cancer Sci. 2021 Mar;112(3):1026-1037. doi: 10.1111/cas.14796. Epub 2021 Jan 22.
The function of ANO9 in gastrointestinal cancer remains unclear. We investigated the biological behaviors and clinical prognostic values of ANO9 in gastric cancer (GC). Knockdown experiments were performed on human GC cell lines using ANO9 siRNA. Eighty-four primary tissue samples from patients with advanced GC were examined immunohistochemically (IHC). Knockdown of ANO9 reduced the progression of cancer cells in MKN7 and MKN74 cells. A microarray analysis revealed that ANO9 regulated PD-L2 via interferon (IFN)-related genes. We confirmed using flow cytometry that the depletion of ANO9 reduced the binding ability to PD-1 by downregulating the expression of PD-L2 in MKN7 and MKN74 cells. IHC revealed a correlation between the expression of ANO9 and PD-L2 and also that the strong expression of ANO9 was an independent poor prognostic factor in patients with advanced GC. The present results indicate that ANO9 regulates PD-L2 and binding ability to PD-1 via IFN-related genes in GC. Therefore, ANO9 has potential as a biomarker and target of immune checkpoint blockage (ICB) for GC.
ANO9 在胃肠道癌症中的功能尚不清楚。我们研究了 ANO9 在胃癌（GC）中的生物学行为和临床预后价值。使用 ANO9 siRNA 对人 GC 细胞系进行了敲低实验。对 84 例晚期 GC 患者的原发性组织样本进行了免疫组织化学（IHC）检查。ANO9 的敲低降低了 MKN7 和 MKN74 细胞中癌细胞的进展。微阵列分析显示 ANO9 通过干扰素（IFN）相关基因调节 PD-L2。我们通过流式细胞术证实，通过下调 MKN7 和 MKN74 细胞中 PD-L2 的表达，ANO9 的耗竭降低了与 PD-1 的结合能力。IHC 显示 ANO9 的表达与 PD-L2 之间存在相关性，并且在晚期 GC 患者中，ANO9 的强表达是独立的预后不良因素。本研究结果表明，ANO9 通过 IFN 相关基因调节 GC 中的 PD-L2 和与 PD-1 的结合能力。因此，ANO9 具有作为 GC 的免疫检查点阻断（ICB）的生物标志物和靶标的潜力。
Zotero 插件