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醛缩酶B(ALDOB)是透明细胞肾细胞癌的一种预后生物标志物和潜在的免疫治疗靶点。

ALDOB is a prognostic biomarker and a potential immunotherapy target for clear cell renal cell carcinoma.

作者信息

Xu Wu, Wu Dali, Li Cuilian, Yan Lingfei, Peng Bo, Luo Yang, Liu Dawei, Li Qing, Wang Tao

机构信息

Department of Urology, The Fifth Affiliated Hospital, Southern Medical University, Guanzhou, China.

出版信息

PeerJ. 2025 Aug 18;13:e19869. doi: 10.7717/peerj.19869. eCollection 2025.

DOI:10.7717/peerj.19869
PMID:40852386
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12369605/
Abstract

BACKGROUND

Aldolase B (), functioning as a glycolytic enzyme, exhibits a controversial role in malignancies and demonstrates dual potential as both a tumor suppressor and cancer-promoting enzyme. Nevertheless, it is still uncertain if there is a relationship between levels, prognosis, and tumor-infiltrating lymphocytes in clear cell renal cell carcinoma (ccRCC).

OBJECTIVE

This study aims to investigate the prognostic significance of in ccRCC and its potential association with clinicopathological features and tumor immune microenvironment. By integrating multi-database bioinformatics analysis and experimental validation, we seek to elucidate the role of in ccRCC progression and its potential as a predictive biomarker.

METHODS

To ascertain the potential link between level, clinical parameters, and overall survival (OS) in individuals with ccRCC, we employed diverse databases, which include The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), the Human Protein Atlas (HPA) and The University of Alabama at Birmingham Cancer data analysis Portal (UALCAN). Furthermore, an in-depth analysis of the link between tumor-infiltrating immune cells (TIIC) and was carried out using the TIMER database. Immunohistochemistry (IHC) was applied to identify the level in a tissue microarray.

RESULTS

The expression of demonstrated a strong association with pathologic T stage, pathologic N stage, pathologic M stage, histologic grade, and gender. Decreased level was linked to unfavorable disease-specific survival (DSS), progress free interval (PFI), and OS outcomes ( < 0.001). Subsequently, a marked link was observed between level and a heightened presence of infiltrating Treg, Th17 cells, and neutrophils in ccRCC. IHC showed that the level in ccRCC samples was notably diminished relative to that in the adjacent normal tissues.

CONCLUSIONS

As a prospective predictive indicator for individuals with ccRCC, reduced level exhibited strong correlations with clinical characteristics, unfavorable outcomes, and immune infiltration in individuals with ccRCC.

摘要

背景

醛缩酶B()作为一种糖酵解酶,在恶性肿瘤中发挥着有争议的作用,具有作为肿瘤抑制因子和促癌酶的双重潜力。然而,在透明细胞肾细胞癌(ccRCC)中,醛缩酶B水平、预后与肿瘤浸润淋巴细胞之间是否存在关联仍不确定。

目的

本研究旨在探讨醛缩酶B在ccRCC中的预后意义及其与临床病理特征和肿瘤免疫微环境的潜在关联。通过整合多数据库生物信息学分析和实验验证,我们试图阐明醛缩酶B在ccRCC进展中的作用及其作为预测生物标志物的潜力。

方法

为了确定ccRCC患者醛缩酶B水平、临床参数与总生存期(OS)之间的潜在联系,我们使用了多个数据库,包括癌症基因组图谱(TCGA)、基因表达综合数据库(GEO)、人类蛋白质图谱(HPA)和阿拉巴马大学伯明翰分校癌症数据分析门户(UALCAN)。此外,使用TIMER数据库对肿瘤浸润免疫细胞(TIIC)与醛缩酶B之间的联系进行了深入分析。应用免疫组织化学(IHC)方法在组织芯片中鉴定醛缩酶B水平。

结果

醛缩酶B的表达与病理T分期、病理N分期、病理M分期、组织学分级和性别密切相关。醛缩酶B水平降低与不良的疾病特异性生存期(DSS)、无进展生存期(PFI)和OS结果相关(< 0.001)。随后,观察到醛缩酶B水平与ccRCC中浸润性调节性T细胞、辅助性T细胞17和中性粒细胞数量增加之间存在显著联系。免疫组织化学显示,ccRCC样本中的醛缩酶B水平相对于相邻正常组织明显降低。

结论

作为ccRCC患者的一种前瞻性预测指标,醛缩酶B水平降低与ccRCC患者的临床特征、不良预后和免疫浸润密切相关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b46a/12369605/f542c496fc5a/peerj-13-19869-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b46a/12369605/040ec4729ebd/peerj-13-19869-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b46a/12369605/e9a894803b4d/peerj-13-19869-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b46a/12369605/d456487aeb5c/peerj-13-19869-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b46a/12369605/2abb612ad98c/peerj-13-19869-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b46a/12369605/af1bac936fc0/peerj-13-19869-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b46a/12369605/3ce070319c0a/peerj-13-19869-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b46a/12369605/450543a21591/peerj-13-19869-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b46a/12369605/cb0fbe5f9ac8/peerj-13-19869-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b46a/12369605/f542c496fc5a/peerj-13-19869-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b46a/12369605/040ec4729ebd/peerj-13-19869-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b46a/12369605/e9a894803b4d/peerj-13-19869-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b46a/12369605/d456487aeb5c/peerj-13-19869-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b46a/12369605/2abb612ad98c/peerj-13-19869-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b46a/12369605/af1bac936fc0/peerj-13-19869-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b46a/12369605/3ce070319c0a/peerj-13-19869-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b46a/12369605/450543a21591/peerj-13-19869-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b46a/12369605/cb0fbe5f9ac8/peerj-13-19869-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b46a/12369605/f542c496fc5a/peerj-13-19869-g009.jpg

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本文引用的文献

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MicroRNA profiling identifies VHL/HIF-2α dependent miR-2355-5p as a key modulator of clear cell Renal cell carcinoma tumor growth.微小RNA分析鉴定出VHL/HIF-2α依赖性的miR-2355-5p作为透明细胞肾细胞癌肿瘤生长的关键调节因子。
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ALDOB suppresses the activity of CD8 T cells in colorectal cancer via the WNT signaling pathway.醛缩酶B通过WNT信号通路抑制结直肠癌中CD8 T细胞的活性。
Immunol Cell Biol. 2025 Mar;103(3):307-316. doi: 10.1111/imcb.12853. Epub 2025 Feb 5.
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Loss of glomerular aldolase B in diabetic nephropathy promotes renal fibrosis via activating Akt/GSK/β-catenin axis.
糖尿病肾病中肾小球醛缩酶B的缺失通过激活Akt/GSK/β-连环蛋白轴促进肾纤维化。
J Adv Res. 2024 Dec 24. doi: 10.1016/j.jare.2024.12.027.
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Diverse roles of aldolase enzymes in cancer development, drug resistance and therapeutic approaches as moonlighting enzymes.醛缩酶在癌症发展、耐药性和作为兼职酶的治疗方法中的多种作用。
Med Oncol. 2024 Aug 9;41(9):224. doi: 10.1007/s12032-024-02470-x.
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Renal cell carcinoma.肾细胞癌。
Lancet. 2024 Aug 3;404(10451):476-491. doi: 10.1016/S0140-6736(24)00917-6. Epub 2024 Jul 18.
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CBX4 suppresses CD8 T cell antitumor immunity by reprogramming glycolytic metabolism.CBX4 通过重编程糖酵解代谢来抑制 CD8 T 细胞抗肿瘤免疫。
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Molecular mechanism of ferroptosis and its application in the treatment of clear cell renal cell carcinoma.铁死亡分子机制及其在肾透明细胞癌治疗中的应用。
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ALDOB/KAT2A interactions epigenetically modulate TGF-β expression and T cell functions in hepatocellular carcinogenesis.醛缩酶B(ALDOB)/赖氨酸乙酰转移酶2A(KAT2A)相互作用在肝细胞癌发生过程中通过表观遗传调控转化生长因子-β(TGF-β)表达及T细胞功能。
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Pan-cancer analysis of aldolase B gene as a novel prognostic biomarker for human cancers.泛癌症分析醛缩酶 B 基因作为人类癌症的新型预后生物标志物。
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