Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Department of Surgical Pathology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Ann Surg Oncol. 2022 Dec;29(13):8677-8687. doi: 10.1245/s10434-022-12384-5. Epub 2022 Aug 16.
NADPH oxidases (NOXs) are transmembrane proteins that generate reactive oxygen species. Recent studies have reported that NOXs are involved in tumor progression in various cancers. However, the expression and role of NOX2 in esophageal squamous cell carcinoma (ESCC) remain unclear. This study aimed to clarify the pathophysiologic role of NOX2 in patients with ESCC and cell lines.
Two human ESCC cell lines (TE5 and KYSE170) were used for NOX2 transfection experiments, and the effects on cell proliferation, cell cycle, cell motility, and cell survival were analyzed. An mRNA microarray analysis was also performed to assess gene expression profiles. Additionally, NOX2 immunohistochemistry was performed on 130 primary ESCC tumor samples to assess the prognostic value of NOX2 in patients with ESCC.
NOX2 depletion significantly inhibited cell proliferation with the G/G arrest and resulted in apoptosis in two cell lines. Microarray analysis revealed a strong relationship between NOX2 gene expression and the signaling pathway of cell cycle regulation by the B-cell translocation gene 2 (BTG2) family, including BTG2, CCNE2, E2F1, and CDK2 genes. Immunohistochemical staining revealed that high NOX2 protein expression was significantly associated with deeper tumor invasion and selected as one of the independent prognostic factors associated with the 5-year OS rate in patients with ESCC.
NOX2 expression in ESCC cells affects tumorigenesis, especially cell cycle progression via the BTG2-related signaling pathway, as well as the prognosis of patients with ESCC. NOX2 may be a novel biomarker and therapeutic target for ESCC.
NADPH 氧化酶（NOXs）是一种跨膜蛋白，可产生活性氧物质。最近的研究报告称，NOXs 参与了多种癌症中的肿瘤进展。然而，NOX2 在食管鳞状细胞癌（ESCC）中的表达和作用仍不清楚。本研究旨在阐明 NOX2 在 ESCC 患者和细胞系中的病理生理作用。
使用两种人 ESCC 细胞系（TE5 和 KYSE170）进行 NOX2 转染实验，分析对细胞增殖、细胞周期、细胞迁移和细胞存活的影响。还进行了 mRNA 微阵列分析以评估基因表达谱。此外，对 130 例原发性 ESCC 肿瘤样本进行了 NOX2 免疫组织化学染色，以评估 NOX2 在 ESCC 患者中的预后价值。
NOX2 耗竭显着抑制了两种细胞系的细胞增殖，导致 G/G 期停滞和细胞凋亡。微阵列分析显示，NOX2 基因表达与细胞周期调控的 B 细胞易位基因 2（BTG2）家族的信号通路之间存在很强的关系，包括 BTG2、CCNE2、E2F1 和 CDK2 基因。免疫组织化学染色显示，高 NOX2 蛋白表达与肿瘤侵袭深度显着相关，并被选为与 ESCC 患者 5 年 OS 率相关的独立预后因素之一。
ESCC 细胞中的 NOX2 表达通过与 BTG2 相关的信号通路影响肿瘤发生，特别是细胞周期进展，以及 ESCC 患者的预后。NOX2 可能是 ESCC 的一种新的生物标志物和治疗靶标。
