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乳酸脱氢酶 A 是一种与子宫内膜癌免疫浸润、m6A 修饰和铁死亡相关的诊断生物标志物

英文原题:Lactate dehydrogenase A is a diagnostic biomarker associated with immune infiltration, m6A modification and ferroptosis in endometrial cancer.

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Lactate dehydrogenase A is a diagnostic biomarker associated with immune infiltration, m6A modification and ferroptosis in endometrial cancer.

PubMed 2024/11/08(内容时间) Front Oncol Q2 · IF 3.4(JCR 2025)

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研究概要

LDHA 有潜力作为 EC 的生物标志物,与 TILs、m6A 修饰和铁死亡相关。

研究思路结论见上方概要

乳酸脱氢酶A(LDHA)已被证实是多种癌症的肿瘤促进因子,但其在子宫内膜癌中的作用仍不清楚。

癌症基因组图谱(TCGA)、定量实时聚合酶链反应和人类蛋白质图谱被用于分析LDHA在EC中的表达。基于TCGA队列,比较了不同临床特征患者的LDHA水平。通过R语言对LDHA相关基因进行了基因组本体论、京都基因与基因组百科全书和基因集富集分析。通过体外实验检测了LDHA敲低对细胞增殖、凋亡、迁移和侵袭的影响。通过肿瘤免疫估计资源2.0和基因表达谱交互分析探索了LDHA表达与免疫浸润之间的关系。基于TCGA-UCEC和GEO队列,研究了LDHA水平与N6-甲基腺苷(m6A)修饰和铁死亡之间的关联。

LDHA在EC组织和EC细胞系中过表达,对EC诊断具有较高的预测准确性。LDHA水平与年龄、组织学类型、组织学分级和放疗相关。LDHA相关基因参与多种生物学功能和信号通路。LDHA下调显著促进细胞凋亡,抑制EC细胞的增殖、迁移和侵袭。LDHA表达与多种TIL(肿瘤浸润淋巴细胞)、m6A相关基因和铁死亡相关基因相关。

展开英文摘要原文

Lactate dehydrogenase A (LDHA) has been confirmed as a tumor promoter in various cancers, but its role in endometrial cancer remains unclear.

The Cancer Genome Atlas (TCGA), quantitative real-time polymerase chain reaction and the Human Protein Atlas were utilized to analyzed the LDHA expression in EC. The LDHA levels of patients with different clinical features were compared based on the TCGA cohort. The Genome Ontology, Kyoto Encyclopedia of Genes and Genomes, and Gene Set Enrichment Analysis of LDHA-related genes were conducted by R language. The influence of LDHA knockdown on cell proliferation, apoptosis, migration and invasion was detected by in vitro experiment. The relationship between LDHA expression and immune infiltration was explored by Tumor Immune Estimation Resource 2.0 and Gene Expression Profiling Interactive Analysis. The association of LDHA level with N6-methyladenosine (m6A) modification and ferroptosis was investigated based on the TCGA-UCEC and the GEO cohort.

The LDHA was overexpressed in EC tissues and EC cell lines, and had high predictive accuracy for the EC diagnosis. The LDHA level was associated with age, histological type, histologic grade, and radiation therapy. LDHA-related genes participated in multiple biological functions and signaling pathways. LDHA downregulation significantly promoted cell apoptosis and inhibited the proliferation, migration, and invasion of EC cells. LDHA expression was connected to multiple tumor-infiltrating lymphocytes (TILs), m6A-related genes, and ferroptosis-related genes.

LDHA has the potential to work as an EC biomarker associated with TILs, m6A modification, and ferroptosis in EC.

论文信息

作者
Huang Y、Tang W、Chen L
单位
Department of Gynaecology and Obstetrics, Affiliated Hospital 2 of Nantong University, Nantong First People's Hospital, Nantong, China.China
期刊
Frontiers in oncology2024
原文标识
PubMed 39582531 · DOI 10.3389/fonc.2024.1458344