A systematic pan-cancer analysis identifies LDHA as a novel predictor for immunological, prognostic, and immunotherapy resistance

Sep 21, 2026

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Lactate dehydrogenase A (LDHA), a key glycolysis enzyme, is investigated for its impact on cancer immune surveillance, tumor-associated macrophage transformation, prognosis, and immunotherapy resistance. Using pan-cancer expression profiling, survival assessment, and multi-omics associations, the study links heterogeneous LDHA expression with poor outcomes. LDHA correlates positively with mononuclear/macrophage presence, immune-cell infiltration, tumor microenvironment features, stemness scores, tumor mutation burden, and predicts chemotherapy and immunotherapy sensitivity. Functional validation shows LDHA knockdown reduces lung cancer proliferation and migration.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages19

Reading Time48 min

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Abstract

Introduction

Cancer burden and need for biomarkers

Warburg effect and LDHA in glycolysis

LDHA and immune surveillance

Rationale for pan-cancer analysis

[www.aging-us.com](www.aging-us.com) AGING 2024, Vol. 16, No. 9 Research Paper A systematic pan-cancer analysis identifies LDHA as a novel predictor for immunological, prognostic, and immunotherapy resistance Qiqi Zhang1,2,*, Yuanning Luo1,3,*, Bingshuo Qian4,5,*, Xiuhua Cao6, Caijun Xu2, Kan Guo1,2 Runlan Wan1,3, Yaling Jiang2, Tiecheng Wang4, Zhiqiang Mei1,2, Jinbiao Liu7, Chaoxiang Lv1,2,4 1The Research Center for Preclinical Medicine, Southwest Medical University, Luzhou, P. R. China 2Southwest Medical University, Luzhou, P. R. China 3 Department of Oncology, The Affiliated Hospital of Southwest Medical University, Luzhou, P. R. China 4Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun , P. R. China 5School of Pharmacy, Henan University, Kaifeng, P. R. China 6 Department of Gastroenterology, The Affiliated Hospital of Southwest Medical University, Luzhou, P. R. China 7Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou, P. R. China *Equal contribution Correspondence to: Zhiqiang Mei, Jinbiao Liu, Chaoxiang Lv; email: [xuguangyin1@163.com](xuguangyin1@163.com), [https://orcid.org/0000-0001-](https://orcid.org/0000-0001-)[ ](https://orcid.org/0000-0001-)5082-214X; [ljb@yzu.edu.cn](ljb@yzu.edu.cn); [lvchaoxiang@126.com](lvchaoxiang@126.com), [https://orcid.org/0000-0002-0199-3169](https://orcid.org/0000-0002-0199-3169) [Keywords:](Keywords: LDHA)[ LDHA](Keywords: LDHA), pan-cancer, single-cell RNA-Seq, tumor microenvironment, immunotherapy Received: August 31, 2023 Accepted: March 18, 2024 Published: May 3, 2024 Copyright: © 2024 Zhang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. ABSTRACT Lactate dehydrogenase A (LDHA), a critical enzyme involved in glycolysis, is broadly involved multiple biological functions in human cancers. It is reported that LDHA can impact tumor immune surveillance and induce the transformation of tumor-associated macrophages, highlighting its unnoticed function of LDHA in immune system. However, in human cancers, the role of LDHA in prognosis and immunotherapy hasn’t been investigated. In this study, we analyzed the expression pattern and prognostic value of LDHA in pan-cancer and explored its association between tumor microenvironment (TME), immune infiltration subtype, stemness scores, tumor mutation burden (TMB), and immunotherapy resistance. We found that LDHA expression is tumor heterogeneous and that its high expression is associated with poor prognosis in multiple human cancers. In addition, LDHA expression was positively correlated with the presence of mononuclear/macrophage cells, and also promoted the infiltration of a range of immune cells. Genomic alteration of LDHA was common in different types of cancer, while with prognostic value in pan-cancers. Pancancer analysis revealed that the significant correlations existed between LDHA expression and tumor microenvironment (including stromal cells and immune cells) as well as stemness scores (DNAss and RNAss) across cancer types. Drug sensitivity analysis also revealed that LDHA was able to predict response to chemotherapy and immunotherapy. Furthermore, it was confirmed that knockdown of LDHA reduced proliferation and migration ability of lung cancer cells. Taken together, LDHA could serve as a prognostic biomarker and a potential immunotherapy marker. 8000 INTRODUCTION Cancer is a leading cause of death in the world and hasan important burden on the quality of life for patients [1–3] . Unluckily, the morbidity and mortality of cancer are increasing rapidly in most countries including North America and Europe [4, 5], and the current medical conditions cannot fully cure it yet. B

FAQs

What role does LDHA play in cancer metabolism and immune-related processes?

LDHA drives glycolysis by converting pyruvate to lactic acid, contributing to acidic microenvironments that support tumor progression. The study also connects LDHA to tumor immune surveillance and to tumor-associated macrophage transformation.

How does LDHA expression relate to prognosis across multiple cancers?

LDHA expression is tumor heterogeneous, and higher LDHA levels are associated with poor prognosis in multiple human cancers in the pan-cancer analysis.

How is LDHA linked to immunotherapy resistance and treatment response?

LDHA expression correlates with immune infiltration and tumor microenvironment features, and drug sensitivity analyses indicate LDHA can predict response to chemotherapy and immunotherapy. The study concludes LDHA is a potential immunotherapy marker.

Sep 21, 2026

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