AKR1B10在肝细胞癌中的表达特征及其与临床病理特征和免疫微环境的相关性
AKR1B10 expression characteristics in hepatocellular carcinoma and its correlation with clinicopathological features and immune microenvironment.
发表日期:2024 May 27
作者:
Li-Na Ma, Yan Ma, Xia Luo, Zi-Min Ma, Li-Na Ma, Xiang-Chun Ding
来源:
CYTOKINE & GROWTH FACTOR REVIEWS
摘要:
肝细胞癌(HCC)是全球主要的健康威胁,其发病机制多样且复杂。醛酮还原酶家族 1 成员 B10 (AKR1B10) 是一种肿瘤相关酶,在多种癌症中表现出异常表达。然而,人们对 AKR1B10 在 HCC 中的作用缺乏全面的了解。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,进一步探讨其在HCC中的作用和潜在的调控机制。这项研究使用各种生物信息学工具和数据库进行了全面分析。最初,从GEO数据库中鉴定出与HCC相关的差异表达基因,并使用TIMER和GEPIA数据库比较HCC和其他癌症中AKR1B10的表达,并使用HPA数据库验证其在HCC组织样本中的特异性。此外,利用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,利用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,识别调节AKR1B10表达的微小RNA(miRNA)和长非编码RNA(lncRNA)以探索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。潜在的监管机制。 AKR1B10 表达升高与 HCC 组织中的性别、原发肿瘤大小和纤维化阶段显着相关。高 AKR1B10 表达表明预后不良,可作为患者预后的独立预测因子。详细的机制分析揭示了 AKR1B10 高表达、免疫细胞浸润和促炎细胞因子之间的正相关性,表明潜在的 DANCR-miR-216a-5p-AKR1B10 轴调节肿瘤微环境并影响 HCC 的发展和预后。 HCC 中 AKR1B10 的高表达不仅与重要的临床病理特征相关,还可能通过激活关键信号通路和改变肿瘤免疫微环境来影响 HCC 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,并强调了其作为生物标志物和治疗靶点的潜力。© 2024。作者。
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.© 2024. The Author(s).