Zhou Fei-Fei, Huang Rong, Jiang Jun, Zeng Xiao-Hong, Zou Shu-Qian
Department of Thoracoabdominal Radiotherapy, Cancer Center, The First People's Hospital of Foshan, Foshan, Guangdong, People's Republic China.
Saudi J Gastroenterol. 2018 Sep-Oct;24(5):301-306. doi: 10.4103/sjg.SJG_46_18.
BACKGROUND/AIMS: COX2 and HER2 are shown to be critical in the regulation of cancer progression. However, the prognostic value of nuclear COX2 in colorectal cancer (CRC) and its relationship with HER2 still remains unknown. In this study, the expression and biological significance of COX2 and HER2 were evaluated in CRC at mRNA and protein levels.
RNA-Seq data of CRC were downloaded from TCGA, and 229 CRC and 50 non-cancerous subjects were enrolled in this study. Bioinformatics and immunohistochemistry analysis was performed based on the obtained data. Survival analysis was conducted to identify factors associated with overall survival of CRC patients.
We showed that mRNA and protein levels of COX2 and HER2 were upregulated in CRC compared with the adjacent tissues. COX2 protein levels and nuclear COX2 expression were correlated with a poor prognosis of CRC patients. In addition, we also revealed that nuclear COX2 expression was positively associated with HER2 expression. Non-nuclear COX2 combined with low HER2 expression, was negatively correlated with Duke's stage and lymph node metastasis, predicting the best outcomes for CRC patients. In addition, our data indicated that non-nuclear COX2 combined with low HER2 expression is an independent prognostic factor for CRC after surgical resection.
The study suggests that nuclear COX2 in combination with HER2 can serve as potential biomarkers for the clinical diagnosis and prognosis of CRC, and targeted inhibition of COX2 and HER2 might be an alternative strategy for the management of CRC.
背景/目的：COX2和HER2在癌症进展调控中起着关键作用。然而，核COX2在结直肠癌（CRC）中的预后价值及其与HER2的关系仍不清楚。在本研究中，我们在mRNA和蛋白质水平评估了COX2和HER2在CRC中的表达及生物学意义。
从TCGA下载CRC的RNA-Seq数据，本研究纳入了229例CRC患者和50例非癌受试者。基于所获数据进行生物信息学和免疫组化分析。进行生存分析以确定与CRC患者总生存相关的因素。
我们发现，与相邻组织相比，CRC中COX2和HER2的mRNA及蛋白质水平上调。COX2蛋白水平和核COX2表达与CRC患者的不良预后相关。此外，我们还发现核COX2表达与HER2表达呈正相关。非核COX2与低HER2表达相结合，与杜克分期和淋巴结转移呈负相关，预示着CRC患者的最佳预后。此外，我们的数据表明，非核COX2与低HER2表达相结合是CRC手术切除后的独立预后因素。
本研究提示，核COX2与HER2联合可作为CRC临床诊断和预后的潜在生物标志物，靶向抑制COX2和HER2可能是CRC治疗的一种替代策略。
