Ningxia Medical University, Yinchuan, 750004, Ningxia, China.
Department of Infectious Disease, General Hospital of Ningxia Medical University, 804 Shengli South Street, Xingqing District, Yinchuan, 750004, Ningxia, China.
Sci Rep. 2024 May 27;14(1):12149. doi: 10.1038/s41598-024-62323-5.
Hepatocellular carcinoma (HCC) represents a major global health threat with diverse and complex pathogenesis. Aldo-keto reductase family 1 member B10 (AKR1B10), a tumor-associated enzyme, exhibits abnormal expression in various cancers. However, a comprehensive understanding of AKR1B10's role in HCC is lacking. This study aims to explore the expression characteristics of AKR1B10 in HCC and its correlation with clinicopathological features, survival prognosis, and tumor immune microenvironment, further investigating its role and potential regulatory mechanisms in HCC. This study conducted comprehensive analyses using various bioinformatics tools and databases. Initially, differentially expressed genes related to HCC were identified from the GEO database, and the expression of AKR1B10 in HCC and other cancers was compared using TIMER and GEPIA databases, with validation of its specificity in HCC tissue samples using the HPA database. Furthermore, the relationship of AKR1B10 expression with clinicopathological features (age, gender, tumor size, staging, etc.) of HCC patients was analyzed using the TCGA database's LIHC dataset. The impact of AKR1B10 expression levels on patient prognosis was evaluated using Kaplan-Meier survival analysis and the Cox proportional hazards model. Additionally, the correlation of AKR1B10 expression with tumor biology-related signaling pathways and tumor immune microenvironment was studied using databases like GSEA, Targetscan, and others, identifying microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) that regulate AKR1B10 expression to explore potential regulatory mechanisms. Elevated AKR1B10 expression was significantly associated with gender, primary tumor size, and fibrosis stage in HCC tissues. High AKR1B10 expression indicated poor prognosis and served as an independent predictor for patient outcomes. Detailed mechanism analysis revealed a positive correlation between high AKR1B10 expression, immune cell infiltration, and pro-inflammatory cytokines, suggesting a potential DANCR-miR-216a-5p-AKR1B10 axis regulating the tumor microenvironment and impacting HCC development and prognosis. The heightened expression of AKR1B10 in HCC is not only related to significant clinical-pathological traits but may also influence HCC progression and prognosis by activating key signaling pathways and altering the tumor immune microenvironment. These findings provide new insights into the role of AKR1B10 in HCC pathogenesis and highlight its potential as a biomarker and therapeutic target.
肝细胞癌（HCC）是一种主要的全球健康威胁，具有多种复杂的发病机制。醛酮还原酶家族 1 成员 B10（AKR1B10）是一种肿瘤相关酶，在各种癌症中表现出异常表达。然而，对于 AKR1B10 在 HCC 中的作用仍缺乏全面的了解。本研究旨在探讨 AKR1B10 在 HCC 中的表达特征及其与临床病理特征、生存预后和肿瘤免疫微环境的相关性，进一步研究其在 HCC 中的作用和潜在调控机制。本研究使用多种生物信息学工具和数据库进行了综合分析。首先，从 GEO 数据库中鉴定与 HCC 相关的差异表达基因，并使用 TIMER 和 GEPIA 数据库比较 AKR1B10 在 HCC 和其他癌症中的表达，使用 HPA 数据库验证其在 HCC 组织样本中的特异性。此外，使用 TCGA 数据库的 LIHC 数据集分析 AKR1B10 表达与 HCC 患者临床病理特征（年龄、性别、肿瘤大小、分期等）的关系。使用 Kaplan-Meier 生存分析和 Cox 比例风险模型评估 AKR1B10 表达水平对患者预后的影响。此外，使用 GSEA、Targetscan 等数据库研究 AKR1B10 表达与肿瘤生物学相关信号通路和肿瘤免疫微环境的相关性，鉴定调控 AKR1B10 表达的 microRNAs（miRNAs）和长非编码 RNA（lncRNAs），以探讨潜在的调控机制。在 HCC 组织中，AKR1B10 表达的升高与性别、原发肿瘤大小和纤维化分期显著相关。高 AKR1B10 表达提示预后不良，是患者结局的独立预测因素。详细的机制分析显示，高 AKR1B10 表达与免疫细胞浸润和促炎细胞因子呈正相关，提示存在一个潜在的 DANCR-miR-216a-5p-AKR1B10 轴调节肿瘤微环境，影响 HCC 的发生和发展及预后。AKR1B10 在 HCC 中的高表达不仅与显著的临床病理特征有关，而且可能通过激活关键信号通路和改变肿瘤免疫微环境影响 HCC 的进展和预后。这些发现为 AKR1B10 在 HCC 发病机制中的作用提供了新的见解，并强调其作为生物标志物和治疗靶点的潜力。
