Fang Tianxing, Hu Liyu, Chen Tianshun, Li Fei, Yang Liu, Liang Bin, Wang Wenjun, Zeng Fancai
Department of Nuclear Medicine, Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, People's Republic of China.
Nuclear Medicine and Molecular Imaging Key Laboratory of Sichuan Province, Luzhou, Sichuan, People's Republic of China.
Breast Cancer (Dove Med Press). 2025 Feb 12;17:157-170. doi: 10.2147/BCTT.S502670. eCollection 2025.
Breast cancer (BC) has become the main malignant tumor threatening the health of women worldwide. Previous studies have reported that Lactate dehydrogenase-A (LDHA) has critical roles in cancer development and progression. We aimed to explore the roles of LDHA and LDH5 isoenzyme activity in BC, which provides a new insight into LDHA for the treatment of BC.
The expression of LDHA in BC and its relationship with clinicopathological features were obtained from various databases including The Cancer Genome Atlas (TCGA), Human Protein Atlas (HPA), Breast Cancer-Gene Expression Miner (bc-GenExMiner), TNMplot, UALCAN. The Kaplan‒Meier Plotter was used to evaluate the prognostic value of LDHA. Western blot was performed to detect LDHA expression. Agarose gel electrophoresis was performed to detect the activities of LDH isoenzymes. The in vitro proliferation, migration and invasion potentials of BC cells were evaluated using MTT assays, colony formation, wound-healing assay, matrix metalloproteinase assays and transwell assays, respectively. The activities of LDH isoenzymes in serum and tissues were measured in patients with BC and healthy controls.
Compared to normal tissues, LDHA expression was significantly higher in BC tissues. Patients' nodal status, histological types, mutation status and PAM50 subtypes were significant factors influencing the expression. By overexpressing or silencing gene in BT549 cells, it was confirmed that LDHA promoted cell proliferation, migration and invasion. LDH5 isoenzyme activity in patients with BC was higher than healthy controls. The increased activity of LDH5 isoenzymes was induced by overexpression of LDHA in BC. High expression of LDHA was found to be associated with poor prognosis in BC.
LDHA plays a critical role in the progression of BC through the regulation of the activity of LDH5 isoenzyme, indicating that LDHA may serve as a valuable target for BC treatment.
乳腺癌已成为威胁全球女性健康的主要恶性肿瘤。既往研究报道，乳酸脱氢酶A（LDHA）在癌症发生发展过程中起关键作用。我们旨在探讨LDHA及乳酸脱氢酶5（LDH5）同工酶活性在乳腺癌中的作用，为乳腺癌治疗中LDHA的研究提供新的见解。
从多个数据库获取乳腺癌中LDHA的表达情况及其与临床病理特征的关系，这些数据库包括癌症基因组图谱（TCGA）、人类蛋白质图谱（HPA）、乳腺癌基因表达挖掘器（bc-GenExMiner）、TNMplot、UALCAN。使用Kaplan-Meier Plotter评估LDHA的预后价值。采用蛋白质免疫印迹法检测LDHA表达。采用琼脂糖凝胶电泳检测LDH同工酶活性。分别使用MTT法、集落形成实验、伤口愈合实验、基质金属蛋白酶实验和Transwell实验评估乳腺癌细胞的体外增殖、迁移和侵袭能力。检测乳腺癌患者和健康对照者血清及组织中LDH同工酶的活性。
与正常组织相比，乳腺癌组织中LDHA表达显著升高。患者的淋巴结状态、组织学类型、突变状态和PAM50亚型是影响其表达的重要因素。通过在BT549细胞中过表达或沉默基因，证实LDHA促进细胞增殖、迁移和侵袭。乳腺癌患者的LDH5同工酶活性高于健康对照者。乳腺癌中LDHA过表达诱导LDH5同工酶活性增加。发现LDHA高表达与乳腺癌预后不良相关。
LDHA通过调节LDH5同工酶活性在乳腺癌进展中起关键作用，表明LDHA可能是乳腺癌治疗的一个有价值的靶点。
