Gao Yan, Wu Ruimin, Pei Zhijun, Ke Changbin, Zeng Daobing, Li Xiaohui, Zhang Yanmin
Department of Pharmacy, Taihe Hospital, Health Science Center, Xi'an Jiaotong University, Xi'an, 710061, China.
School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an, 710061, P.R. China.
Heliyon. 2024 Mar 27;10(7):e28794. doi: 10.1016/j.heliyon.2024.e28794. eCollection 2024 Apr 15.
Cell Cycle-Associated Protein 1 (CAPRIN1) play an important role in cell proliferation, oxidative stress, and inflammatory response. Nonetheless, its role in tumor immunity and ferroptosis is largely unknown in gastrointestinal cancer patients.
Through comprehensive bioinformatics, we investigate CAPRIN1 expression patterns and its role in diagnosis, functional signaling pathways, tumor immune infiltration and ferroptosis of different gastrointestinal cancer subtypes. Besides, immunohistochemistry (IHC) and immune blot were used to validate our esophagus cancer clinical data. The ferroptotic features of CAPRIN1 were assessed through knockdown assays in esophagus cancer cells.
CAPRIN1 expression was significantly upregulated, correlated with poor prognosis, and served as an independent risk factor for most gastrointestinal cancer. Moreover, CAPRIN1 overexpression positively correlated with gene markers of most infiltrating immune cells, and immune checkpoints. CAPRIN1 knockdown significantly decreased the protein level of major histocompatibility complex class I molecules. We also identified a link between CAPRIN1 and ferroptosis-related genes in gastrointestinal cancer. Knockdown of CAPRIN1 significantly increased the production of lipid reactive oxygen species and malondialdehyde. Inhibition of CAPRIN1 expression promoted ferroptotic cell death induced by RAS-selective lethal 3 and erastin in human esophagus cancer cells.
Collectively, our results demonstrate that CAPRIN1 is aberrantly expressed in gastrointestinal cancer, is associated with poor prognosis, and could potentially influence immune infiltration and ferroptosis.
细胞周期相关蛋白1（CAPRIN1）在细胞增殖、氧化应激和炎症反应中发挥重要作用。然而，其在胃肠道癌患者肿瘤免疫和铁死亡中的作用尚不清楚。
通过综合生物信息学，我们研究了CAPRIN1的表达模式及其在不同胃肠道癌亚型的诊断、功能信号通路、肿瘤免疫浸润和铁死亡中的作用。此外，采用免疫组织化学（IHC）和免疫印迹法验证我们的食管癌临床数据。通过在食管癌细胞中的敲低实验评估CAPRIN1的铁死亡特征。
CAPRIN1表达显著上调，与预后不良相关，并作为大多数胃肠道癌的独立危险因素。此外，CAPRIN1过表达与大多数浸润免疫细胞和免疫检查点的基因标志物呈正相关。CAPRIN1敲低显著降低了主要组织相容性复合体I类分子的蛋白水平。我们还确定了CAPRIN1与胃肠道癌中铁死亡相关基因之间的联系。敲低CAPRIN1显著增加了脂质活性氧和丙二醛的产生。抑制CAPRIN1表达促进了RAS选择性致死3和埃拉斯汀诱导的人食管癌细胞铁死亡。
总体而言，我们的结果表明，CAPRIN1在胃肠道癌中异常表达，与预后不良相关，并可能影响免疫浸润和铁死亡。
