Integrated Transcriptomic Analysis Identifies ENO3 as a Candidate Lactate Metabolism-Associated Biomarker in Colorectal Cancer Metastasis

Background and objectives: Metastasis is the primary cause of mortality in colorectal cancer (CRC), a leading global malignancy. Although metabolic reprogramming is a hallmark of cancer, the stage-associated transcriptional features of metabolic pathways during CRC progression remain incompletely understood. This study aimed to characterize transcriptionally inferred metabolic heterogeneity during CRC progression and identify candidate molecular factors associated with metastasis.

Methods

We performed an integrated transcriptomic analysis using TCGA and GEO datasets and compared metabolic pathway signatures across normal tissues, primary tumors, and metastatic lesions. An exploratory tumor lactate metabolism score (TLMS) was developed using Cox regression and LASSO analysis. Consensus clustering identified metabolic subtypes, and their associations with computationally estimated immune-cell signatures were assessed. The functional consequences of ENO3 loss were preliminarily evaluated using CRISPR/Cas9 knockout, cell proliferation assays, and an NSG tail-vein experimental lung colonization model.