乳酸脱氢酶A在乳腺癌诊疗中的研究进展

doi:10.3877/cma.j.issn.2095-655X.2024.02.012

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摘要乳腺癌是一种高度异质性的恶性肿瘤,现有手段对早期乳腺癌诊断依然有限。乳酸脱氢酶A(LDHA)是参与肿瘤细胞糖酵解的关键酶，与肿瘤生长增殖、免疫逃逸、侵袭转移等恶性进展有关。有研究报道LDHA在乳腺癌中异常高表达，然而，LDHA促进乳腺癌进展的具体原因尚不完全清楚。探讨LDHA与乳腺癌进展之间的分子作用机制，对进一步探索LDHA作为新型诊断标志物、开发新型抗肿瘤药物等具有重要研究价值。笔者结合国内外最新报道，对LDHA在乳腺癌诊疗中的研究进展作一综述。

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关键词 ：乳酸脱氢酶A, 乳腺肿瘤, 糖酵解, Warburg效应

Abstract：Breast cancer is a highly heterogeneous malignant tumor, and the existing means for early breast cancer diagnosis remain limited. Lactate dehydrogenase A (LDHA) is a key enzyme involved in glycolysis in tumor cells, which is associated with malignant progression such as tumor growth and proliferation, immune escape, and invasion and metastasis. It has been reported that LDHA is abnormally highly expressed in breast cancer. However, the specific reasons why LDHA promotes breast cancer progression are not fully understood. Exploring the molecular mechanism between LDHA and breast cancer progression is of great value to the future exploration of LDHA as a new diagnostic marker and the development of new anti-tumor drugs. In this paper, the author summarizes the research progress of LDHA in breast cancer diagnosis and treatment based on the latest reports from home and abroad.

Key words： Lactate dehydrogenase A Breast neoplasms Glycolysis Warburg effect

收稿日期: 2024-01-23

基金资助:山东省医药卫生科技发展计划项目（202104010714）;济宁医学院实践教学教育研究科学项目(JYSJ2020A01）

通讯作者: 刘欢， Email: liuhuan198609@163.com

引用本文:

李易飞李文冉刘欢. 乳酸脱氢酶A在乳腺癌诊疗中的研究进展[J]. 中华诊断学电子杂志, 2024, 12(2): 128-132.
Li Yifei, Li Wenran, Liu Huan. Advances in the study of lactate dehydrogenase A in breast cancer diagnosis and treatment. zhzdx, 2024, 12(2): 128-132.

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［1］Siegel RL,Giaquinto AN,Jemal A.Cancer statistics,2024［J］.CA Cancer J Clin,2024,74(1):12-49.DOI：10.3322/caac.21820. ［2］Feng RM,Zong YN,Cao SM,et al.Current cancer situation in China：good or bad news from the 2018 Global Cancer Statistics?［J］.Cancer Commun (Lond),2019,39(1):22.DOI：10.1186/s40880-019-0368-6. ［3］Pavlova NN,Zhu J,Thompson CB.The hallmarks of cancer metabolism：still emerging［J］.Cell Metab,2022,34(3):355-377.DOI：10.1016/j.cmet.2022.01.007. ［4］Warburg O.On the origin of cancer cells［J］.Science,1956,123(3191)：309-314.DOI：10.1126/science.123.3191.309. ［5］Martínez-Reyes I,Chandel NS.Cancer metabolism：looking forward［J］.Nat Rev Cancer,2021,21(10):669-680.DOI：10.1038/s41568-021-00378-6. ［6］Feng Y,Xiong Y,Qiao T,et al.Lactate dehydrogenase A：a key player in carcinogenesis and potential target in cancer therapy［J］.Cancer Med,2018,7(12):6124-6136.DOI：10.1002/cam4.1820. ［7］Claps G,Faouzi S,Quidville V,et al.The multiple roles of LDH in cancer［J］.Nat Rev Clin Oncol,2022,19(12):749-762.DOI：10.1038/s41571-022-00686-2. ［8］Wu HF,Liu H,Zhang ZW,et al.CENPE and LDHA were potential prognostic biomarkers of chromophobe renal cell carcinoma［J］.Eur J Med Res,2023,28(1):481.DOI：10.1186/s40001-023-01449-0. ［9］Wu C,Zheng C,Chen S,et al.FOXQ1 promotes pancreatic cancer cell proliferation,tumor stemness,invasion and metastasis through regulation of LDHA-mediated aerobic glycolysis［J］.Cell Death Dis,2023,14(10):699.DOI：10.1038/s41419-023-06207-y. ［10］Chen J,Wu F,Cao Y,et al.The novel role of LDHA/LDHB in the prognostic value and tumor-immune infiltration in clear cell renal cell carcinoma［J］.PeerJ,2023（11）:e15749.DOI：10.7717/peerj.15749. ［11］Xiao X,Huang X,Ye F,et al.The miR-34a-LDHA axis regulates glucose metabolism and tumor growth in breast cancer［J］.Sci Rep,2016（6）:21735.DOI：10.1038/srep21735. ［12］Rizwan A,Serganova I,Khanin R,et al.Relationships between LDH-A,lactate,and metastases in 4T1 breast tumors［J］.Clin Cancer Res,2013,19(18):5158-5169.DOI：10.1158/1078-0432.CCR-12-3300. ［13］Serganova I,Cohen IJ,Vemuri K,et al.LDH-A regulates the tumor microenvironment via HIF-signaling and modulates the immune response［J］.PLoS One,2018,13(9):e0203965.DOI：10.1371/journal.pone.0203965. ［14］Karami Fath M,Garousi S,Mottahedi M,et al.The role of hypoxia-inducible factors in breast cancer stem cell specification［J］.Pathol Res Pract,2023（243）:154349.DOI：10.1016/j.prp.2023.154349. ［15］Yu JM,Sun W,Wang ZH,et al.TRIB3 supports breast cancer stemness by suppressing FOXO1 degradation and enhancing SOX2 transcription［J］.Nat Commun,2019,10(1):5720.DOI：10.1038/s41467-019-13700-6. ［16］Brooks MD,Burness ML,Wicha MS.Therapeutic implications of cellular heterogeneity and plasticity in breast cancer［J］.Cell Stem Cell,2015,17(3):260-271.DOI：10.1016/j.stem.2015.08.014. ［17］Wang S,Ma L,Wang Z,et al.Lactate dehydrogenase-a (LDH-A) preserves cancer stemness and recruitment of tumor-associated macrophages to promote breast cancer progression［J］.Front Oncol,2021（11）:654452.DOI：10.3389/fonc.2021.654452. ［18］Allison SJ,Knight JR,Granchi C,et al.Identification of LDH-A as a therapeutic target for cancer cell killing via (i) p53/NAD(H)-dependent and (ii) p53-independent pathways［J］.Oncogenesis,2014,3(5):e102.DOI：10.1038/oncsis.2014.16. ［19］Chung TW,Kim EY,Han CW,et al.Machilin a inhibits tumor growth and macrophage M2 polarization through the reduction of lactic acid［J］.Cancers (Basel),2019,11(7).DOI：10.3390/cancers11070963. ［20］Le A,Cooper CR,Gouw AM,et al.Inhibition of lactate dehydrogenase A induces oxidative stress and inhibits tumor progression［J］.Proc Natl Acad Sci U S A,2010,107(5):2037-2042.DOI：10.1073/pnas.0914433107. ［21］Wang S,Yu G,Wang Z,et al.Enhanced antitumor efficacy by a cascade of reactive oxygen species generation and drug release［J］.Angew Chem Int Ed Engl,2019,58(41)：14758-14763.DOI：10.1002/anie.201908997. ［22］Wang ZY,Loo TY,Shen JG,et al.LDH-A silencing suppresses breast cancer tumorigenicity through induction of oxidative stress mediated mitochondrial pathway apoptosis［J］.Breast Cancer Res Treat,2012,131(3):791-800.DOI：10.1007/s10549-011-1466-6. ［23］赵雪可,李威,刘文,等.LDHA对乳腺癌演变的影响及SUMO化修饰［J］.临床与实验病理学杂志,2022,38(4):427-431.DOI：10.13315/j.cnki.cjcep.2022.04.008. ［24］李帅杰,黄晓嘉,肖祥胜,等.LDHA在乳腺癌组织中的表达及其临床意义［J］.中国医师杂志,2017,19(2):207-209.DOI：10.3760/cma.j.issn.1008-1372.2017.02.011. ［25］Feng R,Morine Y,Ikemoto T,et al.Nrf2 activation drive macrophages polarization and cancer cell epithelial-mesenchymal transition during interaction［J］.Cell Commun Signal,2018,16(1):54.DOI：10.1186/s12964-018-0262-x. ［26］Chen P,Zuo H,Xiong H,et al.Gpr132 sensing of lactate mediates tumor-macrophage interplay to promote breast cancer metastasis［J］.Proc Natl Acad Sci U S A,2017,114(3):580-585.DOI：10.1073/pnas.1614035114. ［27］Brand A,Singer K,Koehl GE,et al.LDHA-associated lactic acid production blunts tumor immunosurveillance by T and NK cells［J］.Cell Metab,2016,24(5):657-671.DOI：10.1016/j.cmet.2016.08.011. ［28］丁振罗.LDHA、MCT4和B7-H3在三阴性乳腺癌新辅助化疗疗效评价中的临床意义［D］ .南昌：南昌大学医学部,2023. ［29］Long Y, Gao Z, Hu X, et al. Downregulation of MCT4 for lactate exchange promotes the cytotoxicity of NK cells in breast carcinoma［J］.Cancer Med,2018,7(9):4690-4700.DOI：10.1002/cam4.1713. ［30］Colegio OR,Chu NQ,Szabo AL,et al.Functional polarization of tumour-associated macrophages by tumour-derived lactic acid［J］.Nature,2014,513(7519):559-563.DOI：10.1038/nature13490. ［31］Qian BZ,Li J,Zhang H,et al.CCL2 recruits inflammatory monocytes to facilitate breast-tumour metastasis［J］.Nature,2011,475(7355):222-225.DOI：10.1038/nature10138. ［32］Husain Z,Huang Y,Seth P,et al.Tumor-derived lactate modifies antitumor immune response：effect on myeloid-derived suppressor cells and NK cells［J］.J Immunol,2013,191(3):1486-1495.DOI：10.4049/jimmunol.1202702. ［33］Fischer K,Hoffmann P,Voelkl S,et al.Inhibitory effect of tumor cell-derived lactic acid on human T cells［J］.Blood,2007,109(9):3812-3819.DOI：10.1182/blood-2006-07-035972. ［34］Jin L,Chun J,Pan C,et al.Phosphorylation-mediated activation of LDHA promotes cancer cell invasion and tumour metastasis［J］.Oncogene,2017,36(27):3797-3806.DOI：10.1038/onc.2017.6. ［35］Wu Z,Wu J,Zhao Q,et al.Emerging roles of aerobic glycolysis in breast cancer［J］.Clin Transl Oncol,2020,22(5):631-646.DOI：10.1007/s12094-019-02187-8. ［36］Chen X,Luo R,Zhang Y,et al.Long noncoding RNA DIO3OS induces glycolytic-dominant metabolic reprogramming to promote aromatase inhibitor resistance in breast cancer［J］.Nat Commun,2022,13(1):7160.DOI：10.1038/s41467-022-34702-x. ［37］de la Cruz-López KG,Castro-Muoz LJ,Reyes-Hernández DO,et al.Lactate in the regulation of tumor microenvironment and therapeutic approaches［J］.Front Oncol,2019（9）:1143.DOI：10.3389/fonc.2019.01143. ［38］Giatromanolaki A,Gkegka AG,Pouliliou S,et al.Hypoxia and anaerobic metabolism relate with immunologically cold breast cancer and poor prognosis［J］.Breast Cancer Res Treat,2022,194(1):13-23.DOI：10.1007/s10549-022-06609-0. ［39］Zagami P, Carey LA. Triple negative breast cancer：pitfalls and progress［J］.NPJ Breast Cancer,2022,8(1):95.DOI：10.1038/s41523-022-00468-0. ［40］Doyen J,Trastour C,Ettore F,et al.Expression of the hypoxia-inducible monocarboxylate transporter MCT4 is increased in triple negative breast cancer and correlates independently with clinical outcome［J］.Biochem Biophys Res Commun,2014,451(1):54-61.DOI：10.1016/j.bbrc.2014.07.050. ［41］Liu Q,Guan C,Liu C,et al.Targeting hypoxia-inducible factor-1alpha：a new strategy for triple-negative breast cancer therapy［J］.Biomed Pharmacother,2022（156）:113861.DOI：10.1016/j.biopha.2022.113861. ［42］Brown JE,Cook RJ,Lipton A,et al.Serum lactate dehydrogenase is prognostic for survival in patients with bone metastases from breast cancer：a retrospective analysis in bisphosphonate-treated patients［J］.Clin Cancer Res,2012,18(22):6348-6355.DOI：10.1158/1078-0432.CCR-12-1397. ［43］袁俊.血清AFP、AFU、ALP、GGT、LDH水平联合检测在肝癌诊断中的应用价值［J］.中国民康医学,2023,35(7):108-110.DOI：10.3969/j.issn.1672-0369.2023.07.034. ［44］Hussien R,Brooks GA.Mitochondrial and plasma membrane lactate transporter and lactate dehydrogenase isoform expression in breast cancer cell lines［J］.Physiol Genomics,2011,43(5):255-264.DOI：10.1152/physiolgenomics.00177.2010. ［45］Gottfried E,Lang SA,Renner K,et al.New aspects of an old drug-diclofenac targets MYC and glucose metabolism in tumor cells［J］.PLoS One,2013,8(7):e66987.DOI：10.1371/journal.pone.0066987. ［46］Farabegoli F, Vettraino M, Manerba M, et al. Galloflavin, a new lactate dehydrogenase inhibitor,induces the death of human breast cancer cells with different glycolytic attitude by affecting distinct signaling pathways［J］.Eur J Pharm Sci,2012,47(4):729-738.DOI：10.1016/j.ejps.2012.08.012. ［47］Kim EY,Chung TW,Han CW,et al.A novel lactate dehydrogenase inhibitor,1-(Phenylseleno)-4-(Trifluoromethyl) benzene,suppresses tumor growth through apoptotic cell death［J］.Sci Rep,2019,9(1):3969.DOI：10.1038/s41598-019-40617-3. ［48］Altinoz MA,Ozpinar A.Oxamate targeting aggressive cancers with special emphasis to brain tumors［J］.Biomed Pharmacother,2022（147）:112686.DOI：10.1016/j.biopha.2022.112686. ［49］Das CK,Parekh A,Parida PK,et al.Lactate dehydrogenase A regulates autophagy and tamoxifen resistance in breast cancer［J］.Biochim Biophys Acta Mol Cell Res,2019,1866(6):1004-1018.DOI：10.1016/j.bbamcr.2019.03.004.