Characteristics of Aurora Kinase A-Mediated Tumor Microenvironment in Colorectal Cancer and Mining of Active Compounds From Chinese Herbs
- VernacularTitle:蛋白激酶AURKA介导的大肠癌肿瘤微环境特征及中药有效成分挖掘
- Author:
Mengyao LI
1
;
Dongming HUA
;
Zhiyan WANG
;
Zhiyi LIU
;
Hangjun GONG
;
Yunchuan SUN
;
Xueqing HU
;
Yan WANG
Author Information
- Keywords: Colorectal cancer; Aurora kinase A; Immune microenvironment; Traditional Chinese medicine; Active compound
- From: Journal of Sichuan University (Medical Sciences) 2025;56(1):59-67
- CountryChina
- Language:Chinese
- Abstract: Objective To investigate the effects of Aurora kinase A(AURKA)on the tumor microenvironment of colorectal cancer(CRC)and to predict the active compounds in Chinese herbs that can target AURKA.Methods Based on the transcriptomic data and clinical information from 380 CRC tissues and 51 paracancerous tissues in The Cancer Genome Atlas(TCGA)database,the infiltration of different cells in the tumor tissues was analyzed using xCell and the binding of active compounds of Chinese herbs with AURKA was predicted through molecular docking.Results The expression of AURKA was significantly upregulated in CRC tissues compared with that in paracancerous tissues(P＜0.05),and CRC patients with high AURKA expression had shorter overall survival.Compared with the AURKA low-expression group,the abundance of macrophages,monocytes,and effector memory CD4+and CD8+T cells was significantly downregulated in the AURKA high-expression group(P＜0.05).In addition,the cytotoxicity of T cells was significantly reduced(P＜0.05).Further analysis revealed that AURKA expression was positively correlated with the abundance of myeloid-derived suppressor cells(MDSCs)and the expression levels of their chemokines CXCL2 and CXCL5(P＜0.05).Genes that were differentially expressed between the AURKA high-and low-expression groups were mainly enriched in monocyte migration,chemokine-induced cellular responses,and other related processes.Chinese herbal compounds,including hesperidin,aristololactam A Ⅱ a,anacardic acid,coumestrol,and 17β-estradiol,all showed binding energies to AURKA lower than-1.2 kcal/mol,indicating a certain level of binding stability.Among these Chinese herbal compounds,17β-estradiol exhibited the best binding stability to AURKA-3UOL.Conclusion The high expression of AURKA in CRC tissues suggests a poor clinical prognosis.AURKA can promote the development of a suppressive immune microenvironment in CRC,and 17β-estradiol,an active compound from Chinese herbs,is a potential therapeutic agent targeting AURKA.
