Department of Oncology, Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research & The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, 210009, Jiangsu, China.
Department of Gastroenterology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, 210008, Jiangsu, China.
Hum Cell. 2019 Oct;32(4):487-494. doi: 10.1007/s13577-019-00263-3. Epub 2019 Jul 23.
Paraoxonase-2 (PON2) belongs to the paraoxonase (PON) protein family. Unlike paraoxonase-1 (PON1), the expression and significance of PON2 remained largely unknown in gastric cancer (GC). Thus, the purpose of our study was to investigate the role of PON2 in GC. First, we found PON2 expression was obviously increased in GC samples compared with paired normal tissue samples at The Cancer Genome Atlas (TCGA) database. Then the high expression status of PON2 mRNA and protein in GC tissues was confirmed by RT-qPCR and immunohistochemistry. Furthermore, we performed the immunohistochemical analysis to study the correlation between PON2 expression and clinicopathological parameters of GC patients, and found high PON2 expression had significantly positive association with diffuse type, clinical stage, tumor invasion, lymph node metastasis and distant metastasis in GC patients. Moreover, survival analysis suggested GC patients with high PON2 expression resulted in a remarkably shorter overall survival compared with GC patients with low PON2 expression, and high expression of PON2 acted as an unfavorable predictor for overall survival. The in vitro studies indicated that silencing of PON2 expression inhibited GC cell proliferation, migration and invasion. In conclusion, our findings give first evidence that PON2 serves as oncogene in GC.
对氧磷酶 2（PON2）属于对氧磷酶（PON）蛋白家族。与对氧磷酶 1（PON1）不同，PON2 的表达和意义在胃癌（GC）中仍然很大程度上未知。因此，我们的研究目的是研究 PON2 在 GC 中的作用。首先，我们在癌症基因组图谱（TCGA）数据库中发现 PON2 表达在 GC 样本中明显高于配对的正常组织样本。然后通过 RT-qPCR 和免疫组织化学证实了 GC 组织中 PON2 mRNA 和蛋白的高表达状态。此外，我们进行了免疫组织化学分析，以研究 PON2 表达与 GC 患者临床病理参数之间的相关性，发现 PON2 高表达与 GC 患者弥漫型、临床分期、肿瘤浸润、淋巴结转移和远处转移呈显著正相关。此外，生存分析表明，PON2 高表达的 GC 患者的总生存率明显低于 PON2 低表达的 GC 患者，PON2 的高表达是总生存率的不利预测因素。体外研究表明，沉默 PON2 表达可抑制 GC 细胞的增殖、迁移和侵袭。总之，我们的研究结果首次表明 PON2 在 GC 中是一种癌基因。
