Systematic analysis of the role of LDHs subtype in pan-cancer demonstrates the importance of LDHD in the prognosis of hepatocellular carcinoma patients

Sep 21, 2026

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Background Lactate dehydrogenase (LDHs) enzymes participate in anaerobic glycolysis, including LDHA, LDHB, LDHC and LDHD. Considering their regulatory roles in tumor progression, the study examines LDHs across pan-cancers and evaluates prognostic relevance. Methods employ Cox regression, Kaplan–Meier, ROC analyses and clinical correlations, integrating TCGA and multiple bioinformatics resources, plus cBioPortal and GSEA. Cell experiments in HepG2 and Huh7 test LDHD knockdown or overexpression using proliferation, migration, invasion, and signaling/marker assays. Results show subtype-specific, prognostic and immune-relationship patterns, with LDHD driving distinct HCC phenotypes.

LanguageEnglish

CategoryResearch & Report

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Pages20

Reading Time50 min

AccessFree to download

Abstract

Background

Methods

Results

Conclusion

Introduction

Cancer burden and heterogeneity

Need for biomarkers

Keywords

Wang et al. BMC Cancer (2024) 24:156 [https://doi.org/10.1186/s12885-024-11920-8](https://doi.org/10.1186/s12885-024-11920-8) BMC Cancer RESEARCH Open Access Systematic analysis ofthe role of LDHs subtype in pan-cancer demonstrates the importance of LDHD in the prognosis of hepatocellular carcinoma patients Shengnan Wang1,2,3†, Xingwei Wu1,2,4†, Xiaoming Wu1,2,5, Jin Cheng1,2,6, Qianyi Chen1,2 and Zhilin Qi1,2* Abstract Background Lactate dehydrogenase (LDHs) is an enzyme involved in anaerobic glycolysis, including LDHA, LDHB, LDHC and LDHD. Given the regulatory role in the biological progression of certain tumors, we analyzed the role of LDHs in pan-cancers. Methods Cox regression, Kaplan–Meier curves, Receiver Operating Characteristic (ROC) curves, and correla tion of clinical indicators in tumor patients were used to assess the prognostic significance of LDHs in pan cancer. TheTCGA, HPA, TIMER, UALCAN, TISIDB, and Cellminer databases were used to investigate the correlation between the expression of LDHs and immune subtypes, immune checkpoint genes, methylation levels, tumor mutational load, microsatellite instability, tumor-infiltrating immune cells and drug sensitivity. The cBioPortal database was also used to identify genomic abnormalities of LDHs in pan-cancer. A comprehensive assessment of the biological functions of LDHs was performed using GSEA. In vitro, HepG2 and Huh7 cells were transfected with LDHD siRNA and GFP-LDHD, the proliferation capacity of cells was examined using CCK-8, EdU, and colony formation assays; the migration and invasion of cells was detected by wound healing and transwell assays; western blotting was used to detect the levels of MMP-2, MMP-9, E-cadherin, N-cadherin and Akt phosphorylation. Results LDHs were differentially expressed in a variety of human tumor tissues. LDHs subtypes can act as pro-oncogenes or anti-oncogenes in different types of cancer and have an impact on the prognosis of patients with tumors by influencing their clinicopathological characteristics. LDHs were differentially expressed in tumor immune subtypes and molecular subtypes. In addition, LDHs expression correlated with immune checkpoint genes, tumor mutational load, and microsatellite instability. LDHD was identified to play an important role in the prognosis of HCC patients, according to a comprehensive analysis of LDHs in pan-cancer. In HepG2 and Huh7 cells, knockdown of LDHD promoted cell proliferation, migration, and invasion, promoted the protein expression levels of MMP-2, MMP-9, N-cadherin, and Akt phosphorylation, but inhibited the protein expression level of E-cadherin. In addition, LDHD overexpression showed the opposite changes. †Shengnan Wang and Xingwei Wu these authors have contributed equally to this work. *Correspondence: Zhilin Qi [20010012@wnmc.edu.cn](20010012@wnmc.edu.cn) Full list of author information is available at the end of the article © The Author(s) 2024. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit [http://creativecommons.org/licenses/by/4.0/](http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ()[. The Creative Commons Public Domain Dedication waiver (](http://creat

FAQs

What is the main biological focus of this study?

The study focuses on lactate dehydrogenase (LDHs) subtypes, especially LDHD, and their roles in pan-cancer and hepatocellular carcinoma (HCC) prognosis.

Which analytical methods and data sources are used to assess LDHs prognostic value?

Cox regression, Kaplan–Meier curves, ROC curves, and correlations with clinical indicators are used, alongside TCGA and multiple immune/metabolic analysis databases (e.g., TIMER, UALCAN, TISIDB, Cellminer) plus cBioPortal.

What do the in vitro experiments indicate about LDHD in HCC cells?

LDHD knockdown promotes proliferation, migration, and invasion in HepG2 and Huh7 cells, while LDHD overexpression produces opposite effects, alongside changes in markers related to EMT and Akt signaling.

Sep 21, 2026

Uploaded by Himbo