Wu Anqi, Li Hao, Gao Mengnan, Liang Juan, Huang Jiaqi, Farrés Jaume, Cao Deliang, Li Guoqing
Department of Clinical Research Center, The Second Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, China.
Hunan Province Key Laboratory of Basic and Clinical Pharmacological Research on Gastrointestinal Tumors, The Second Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, China.
Front Immunol. 2024 Dec 6;15:1488042. doi: 10.3389/fimmu.2024.1488042. eCollection 2024.
Aldo-keto reductase 1B10 (AKR1B10) is a multifunctional enzyme, which is important in cancer development and progression, but the landscape of AKR1B10 in pan-cancers and in tumor microenvironment is unclear.
This study integrated the sequencing data of 33 cancer types, including gastric cancer, from TCGA project to explored the expression pattern and genetic and epigenetic alterations of AKR1B10. The association of AKR1B10 expression with clinical progression of cancers was evaluated by Kaplan-Meier analysis; the potential role of AKR1B10 in tumor microenvironment (TME) and immune-related gene expression were analyzed by PURITY, ESTIMATE, TIMER and CIBERSORT algorithms. The expression of AKR1B10 and immune cell markers in gastric cancer were evaluated with multiplex immunofluorescence staining.
Results indicated that AKR1B10 was highly expressed in the gastrointestinal tract in health donors, but the expression of AKR1B10 was significantly changed in most of cancer types, which may be ascribed to DNA methylation in its promoter. The AKR1B10 expression in cancers and its value in disease progression was bidirectional and functionally enriched in metabolism in pan-cancers. In tumor microenvironment, AKR1B10 was significantly correlated with immune cell infiltrations and immune gene expression. In the stomach, along with the diminishing of AKR1B10 expression, CD68+ macrophage increased and CD19+ B cell decreased in gastric cancer.
These data indicates that AKR1B10 may be an important factor in the development and progression and a potential therapeutic target for multiple cancers, but plays as a protector in the gastric tissues.
醛酮还原酶1B10(AKR1B10)是一种多功能酶,在癌症发生和发展过程中起着重要作用,但AKR1B10在泛癌及肿瘤微环境中的情况尚不清楚。
本研究整合了来自TCGA项目的33种癌症类型(包括胃癌)的测序数据,以探究AKR1B10的表达模式、基因及表观遗传改变。通过Kaplan-Meier分析评估AKR1B10表达与癌症临床进展的关联;采用PURITY、ESTIMATE、TIMER和CIBERSORT算法分析AKR1B10在肿瘤微环境(TME)中的潜在作用及免疫相关基因表达。用多重免疫荧光染色评估胃癌中AKR1B10和免疫细胞标志物的表达。
结果表明,AKR1B10在健康供体的胃肠道中高表达,但在大多数癌症类型中其表达发生了显著变化,这可能归因于其启动子中的DNA甲基化。AKR1B10在癌症中的表达及其在疾病进展中的价值具有双向性,且在泛癌中功能上富集于代谢。在肿瘤微环境中,AKR1B10与免疫细胞浸润和免疫基因表达显著相关。在胃中,随着胃癌中AKR1B10表达的降低,CD68+巨噬细胞增加,CD19+B细胞减少。
这些数据表明,AKR1B10可能是癌症发生和发展的重要因素以及多种癌症的潜在治疗靶点,但在胃组织中起保护作用。