Xu Zhijie, Peng Bi, Kang Fanhua, Zhang Wenqin, Xiao Muzhang, Li Jianbo, Hong Qianhui, Cai Yuan, Liu Wei, Yan Yuanliang, Peng Jinwu
Department of Clinical Laboratory, Xiangya Hospital, Central South University, Changsha, China.
Department of Pathology, Xiangya Hospital, Central South University, Changsha, China.
Front Cell Dev Biol. 2022 Jun 9;10:877254. doi: 10.3389/fcell.2022.877254. eCollection 2022.
The different pharmacological effects of drugs in different people can be explained by the polymorphisms of drug metabolism-related genes. Emerging studies have realized the importance of drug metabolism-related genes in the treatment and prognosis of cancers, including ovarian cancer (OV). In this study, using comprehensive bioinformatics and western blot, we identified that the drug metabolism-related gene, ADH1B, was significantly down-regulated in OV cells and tissues. The patients with a high level of ADH1B presented a good prognosis. We also found a negative correlation between ADH1B expression and the activity of chemotherapeutic agents, such as cyclophosphamide. In addition, positive correlations were observed between ADH1B expression and multiple immune checkpoints, including LAG3 and HAVCR2. The immune infiltration analysis further indicated that aberrantly expressed ADH1B might have important roles in regulating the infiltration of macrophages and neutrophils in OV tissues. Then, the co-expression analysis was conducted and the top three enriched KEGG pathways were spliceosome, RNA transport, and DNA replication. In conclusion, the drug metabolism-related gene ADH1B and its interactive network play an essential role in the immune regulation and therapeutic response and maybe identified as promising therapeutic targets for OV patients.
药物在不同个体中产生的不同药理作用可通过药物代谢相关基因的多态性来解释。新兴研究已认识到药物代谢相关基因在包括卵巢癌(OV)在内的癌症治疗和预后中的重要性。在本研究中,我们运用综合生物信息学和蛋白质免疫印迹法,鉴定出药物代谢相关基因ADH1B在OV细胞和组织中显著下调。ADH1B水平高的患者预后良好。我们还发现ADH1B表达与环磷酰胺等化疗药物的活性呈负相关。此外,观察到ADH1B表达与包括LAG3和HAVCR2在内的多个免疫检查点呈正相关。免疫浸润分析进一步表明,异常表达的ADH1B可能在调节OV组织中巨噬细胞和中性粒细胞的浸润方面发挥重要作用。随后进行了共表达分析,富集程度最高的前三个KEGG通路是剪接体、RNA转运和DNA复制。总之,药物代谢相关基因ADH1B及其相互作用网络在免疫调节和治疗反应中起着至关重要的作用,可能被确定为OV患者有前景的治疗靶点。