TITLE:
LDHC as a Novel Tumor-Suppressive Biomarker in Cervical Cancer: Multi-Omics Analysis Reveals Diagnostic and Prognostic Significance
AUTHORS:
Shanshan Xiao, Yuhong Hu, Yawen Li, Xin Zhang, Zijun Xiao, Mingyou Dong, Lusheng Liao
KEYWORDS:
LDH Family, Cervical Squamous Cell Carcinoma (CESC), Biomarker, DNA Methylation, Immune Infiltration, LDHC
JOURNAL NAME:
Journal of Biosciences and Medicines,
Vol.13 No.11,
November
10,
2025
ABSTRACT: This study presents a comprehensive molecular characterization of lactate dehydrogenase (LDH) family members in cervical squamous cell carcinoma (CESC). Through integrated multi-omics analysis of TCGA and GEO datasets, we identified distinct tissue-specific expression patterns, with LDHA and LDHB showing ubiquitous expression while LDHAL6B and LDHC exhibited testis-specific restriction. Pan-cancer analysis revealed significant overexpression of multiple LDH isoforms in CESC and other malignancies, with LDHC demonstrating exceptional diagnostic performance (AUC = 0.950 in TCGA, AUC = 0.884 in GSE63514). Survival analysis established LDHC as a favorable prognostic marker, contrasting with the poor outcomes associated with other LDH isoforms. Functional network analysis revealed LDH family involvement in key metabolic pathways including pyruvate metabolism and glycolysis. Epigenetic regulation was implicated through differential methylation patterns, particularly LDHB hypermethylation and LDHC hypomethylation in tumor tissues. Immune correlation analysis demonstrated significant associations between LDH expression and immune cell infiltration/checkpoint markers. Crucially, functional validation in Hela cells showed that LDHC knockdown enhanced proliferation (CCK-8 assay), colony formation, migration (wound healing), and invasion (Transwell), suggesting a tumor-suppressive role. These findings establish LDHC as a promising diagnostic biomarker and potential therapeutic target in CESC, while highlighting the complex, isoform-specific roles of LDH family members in cervical cancer pathogenesis. Our results provide new insights into metabolic reprogramming in CESC and suggest LDHC may represent a novel protective factor in cervical carcinogenesis.