Abstract
Introduction:
Metabolic reprogramming, characterized by alterations in metabolic pathways to support energy production and biosynthesis, is a hallmark of cancer and is exemplified by the Warburg effect. This process plays a pivotal role in tumor progression and is evident across multiple cancer types, including colorectal cancer (CRC).
Objectives:
This study aimed to investigate the expression profiles of metabolism-related genes in CRC cells at early and advanced stages and to validate the expression of selected genes in CRC tissue samples.
Methods:
Tissues from patients with early and advanced stages of CRC were collected to investigate the expression profiles of metabolism-related genes using microarray analysis. Selected genes were further validated at both the mRNA and protein levels by reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemistry (IHC), respectively. Based on gene profiling from microarray analysis, the metabolism-related gene lactate dehydrogenase A (LDHA) was selected for further investigation. A retrospective evaluation of LDHA expression was conducted using 260 formalin-fixed, paraffin-embedded (FFPE) tissue sections obtained from CRC patients diagnosed between January 2021 and December 2023 at the National Cancer Institute, Thailand.
Results:
Comparative analysis revealed 758 upregulated and 619 downregulated pathways in early-stage CRC and 630 upregulated and 614 downregulated pathways in advanced-stage CRC. From all of these pathways, altered metabolism-related pathways were predominantly associated with glycolysis, oxidative phosphorylation, and CRC metabolic reprogramming. Among metabolism-related genes, LDHA exhibited significantly elevated expression in CRC tissues compared to adjacent normal tissues, with marked increases at both mRNA and protein levels in early and advanced stages. Statistical analysis demonstrated a significant correlation between LDHA expression and metastasis to lymph nodes as well as distant organs, including the lungs and liver.
Conclusions:
These findings suggest that metabolic reprogramming is strongly linked to CRC progression and that LDHA may serve as a promising biomarker for CRC screening, prognosis, and therapeutic intervention.
Keywords:
colorectal cancer; gene expression; lactate dehydrogenase a; ldha; metabolic reprogramming.