Prognostic Value of Lactate Dehydrogenase Expression in Different Cancers: A Meta-Analysis

Lv, Jialun; Zhou, Zijian; Wang, Jingzi; Yu, Hao; Lü, Hongmei; Yuan, Baorui; Han, Jie; Zhou, Rui; Zhang, Xiaolei; Yang, Xiao; Yang, Haiwei; Li, Pengchao; Lü, Qiang

doi:10.1016/j.amjms.2019.09.012

Cited by 27 publications

(22 citation statements)

References 35 publications

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“…Based on the observation that LDH-A is overexpressed in clinical prostate cancer samples (when compared with benign prostate hyperplasia), 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 we developed a LDH-A shRNA KD and control (NC) prostate tumor cell line (MyC-CaP:hPSMA + RLuc-IRES-GFP) in an animal model to study (1) whether significant changes are induced in the TME by LDH-A KD in MyC-CaP:hPSMA + RLuc-IRES-GFP tumors, and (2) whether there is a significant enhancement in the efficacy of second-generation hPSMA CAR-directed T cell therapy in LDH-A downregulated tumors.…”

Section: Discussionmentioning

confidence: 99%

Lactate Dehydrogenase A Depletion Alters MyC-CaP Tumor Metabolism, Microenvironment, and CAR T Cell Therapy

Mane

Cohen

Ackerstaff

et al. 2020

Molecular Therapy - Oncolytics

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To enhance human prostate-specific membrane antigen (hPSMA)-specific chimeric antigen receptor (CAR) T cell therapy in a hPSMA + MyC-CaP tumor model, we studied and imaged the effect of lactate dehydrogenase A (LDH-A) depletion on the tumor microenvironment (TME) and tumor progression. Effective LDH-A short hairpin RNA (shRNA) knockdown (KD) was achieved in MyC-CaP:hPSMA + Renilla luciferase (RLuc)-internal ribosome entry site (IRES)-GFP tumor cells, and changes in tumor cell metabolism and in the TME were monitored. LDH-A downregulation significantly inhibited cell proliferation and subcutaneous tumor growth compared to control cells and tumors. However, total tumor lactate concentration did not differ significantly between LDH-A knockdown and control tumors, reflecting the lower vascularity, blood flow, and clearance of lactate from LDH-A knockdown tumors. Comparing treatment responses of MyC-CaP tumors with LDH-A depletion and/or anti-hPSMA CAR T cells showed that the dominant effect on tumor growth was LDH-A depletion. With anti-hPSMA CAR T cell treatment, tumor growth was significantly slower when combined with tumor LDH-A depletion and compared to control tumor growth (p < 0.0001). The lack of a complete tumor response in our animal model can be explained in part by (1) the lower activity of human CAR T cells against hPSMA-expressing murine tumors in a murine host, and (2) a loss of hPSMA antigen from the tumor cell surface in progressive generations of tumor cells.

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Section: Discussionmentioning

confidence: 99%

Lactate Dehydrogenase A Depletion Alters MyC-CaP Tumor Metabolism, Microenvironment, and CAR T Cell Therapy

Mane

Cohen

Ackerstaff

et al. 2020

Molecular Therapy - Oncolytics

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“…LDHA also known as LDH5, is a key enzyme involving in the glycolysis, and play a vital role in tumor initiation, maintenance, progression, and metastasis [10]. LDHA is reported to be up-regulated in many kinds of cancer, and associated with poor prognosis, including breast cancer [23], colorectal cancer [7], liver cancer [24], bladder cancer [8] and prostate cancer [5,9], etc,. Especially, in the era of immune therapy treatment, serum LDH levels seem also to be associated with the e ciency of PD1/PDL1 e ciency [25].…”

Section: Discussionmentioning

confidence: 99%

“…High metabolism has been recognized as a new hallmark of cancer, and emerged as a potential target for anti-cancer drugs [4]. LDHA is a key enzyme evolved in glycolysis, and has been reported to be upregulated in many kinds of cancer, and associated with poor prognosis [5][6][7][8][9]. Accumulating evidence indicates that LDHA inhibition exhibits promising anti-cancer effects through various mechanisms, as well as synergistically enhances the e cacy of other treatments, including chemotherapy, radiotherapy and target drugs [10,11].…”

Section: Introductionmentioning

confidence: 99%

Targeting Lactate Dehydrogenase A Improves Radiotherapy Efficacy in Non-Small Cell Lung Cancer: From Bedside to Bench

Yang

Chong

Dai

et al. 2021

Preprint

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BackgroundLDHA is overexpressed in many kinds of cancer, and associated with poor prognosis. In the current study, we evaluated the prognostic value of LDHA expression in non-small cell lung cancer (NSCLC), and tested whether LDHA inhibition might improve radiotherapy efficacy in NSCLC.MethodsLDHA mRNA expression was investigated in NSCLC patients, using online database and further verified by immunohistochemistry. The prognostic value of LDHA was evaluated using Kaplan-Meier plotter database. In vitro, two NSCLC cell lines were pretreated with oxamate, an inhibitor of LDHA, and colony formation method was performed to determine cellular radiosensitivity. Comet assay was used to detect DNA damage after irradiation. Flow cytometry was applied to test cell cycle progression and apoptosis, and autophagy was examined by monodansylcadaverin (MDC) staining.ResultsBoth mRNA and protein levels of LDHA expression were up-regulated in NSCLC tissues. High LDHA expression was a poor prognostic factor and associated with radioresistance in NSCLC patients. LDHA inhibition by oxamate remarkably increased radiosensitivity in both A549 and H1975 cancer cells, and enhanced ionizing radiation (IR)-induced apoptosis and autophagy, accompanied by cell cycle distribution alternations. Furthermore, LDHA inhibition induced reactive oxygen species (ROS) accumulation and cellular ATP depletion, which might increase DNA injury and hinder DNA repair activity.ConclusionsOur study suggests inhibition of LDHA may be a potential strategy to improve radiotherapy efficacy in NSCLC patients, which needs to be further tested by clinical trials.

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“…Third, as mentioned by the authors, LDH expression seems to have substantial genetic heterogeneity between Asians and Caucasians 10,11 . Assuming that NH hospitals have a wide range of ethnic patients, further data separated by ethnicity may provide new clues.…”

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confidence: 83%

Li Yan et al. reply

Zhang

Xiao

et al. 2020

Nat Mach Intell

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Prognostic Value of Lactate Dehydrogenase Expression in Different Cancers: A Meta-Analysis

Cited by 27 publications

References 35 publications

Lactate Dehydrogenase A Depletion Alters MyC-CaP Tumor Metabolism, Microenvironment, and CAR T Cell Therapy

Lactate Dehydrogenase A Depletion Alters MyC-CaP Tumor Metabolism, Microenvironment, and CAR T Cell Therapy

Targeting Lactate Dehydrogenase A Improves Radiotherapy Efficacy in Non-Small Cell Lung Cancer: From Bedside to Bench

Li Yan et al. reply

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