Candida albicans and colorectal cancer: A paradoxical role revealed through metabolite profiling and prognostic modeling

Abstract

BACKGROUND

Emerging evidence implicates Candida albicans (C. albicans) in human oncogenesis. Notably, studies have supported its involvement in regulating outcomes in colorectal cancer (CRC). This study investigated the paradoxical role of C. albicans in CRC, aiming to determine whether it promotes or suppresses tumor development, with a focus on the mechanistic basis linked to its metabolic profile.

AIM

To investigate the dual role of C. albicans in the development and progression of CRC through metabolite profiling and to establish a prognostic model that integrates the microbial and metabolic interactions in CRC, providing insights into potential therapeutic strategies and clinical outcomes.

METHODS

A prognostic model integrating C. albicans with CRC was developed, incorporating enrichment analysis, immune infiltration profiling, survival analysis, Mendelian randomization, single-cell sequencing, and spatial transcriptomics. The effects of the C. albicans metabolite mixture on CRC cells were subsequently validated in vitro. The primary metabolite composition was characterized using liquid chromatography-mass spectrometry.

RESULTS

A prognostic model based on five specific mRNA markers, EHD4, LIME1, GADD45B, TIMP1, and FDFT1, was established. The C. albicans metabolite mixture significantly reduced CRC cell viability. Post-treatment analysis revealed a significant decrease in gene expression in HT29 cells, while the expression levels of TIMP1, EHD4, and GADD45B were significantly elevated in HCT116 cells. Conversely, LIME1 expression and that of other CRC cell lines showed reductions. In normal colonic epithelial cells (NCM460), GADD45B, TIMP1, and FDFT1 expression levels were significantly increased, while LIME1 and EHD4 levels were markedly reduced. Following metabolite treatment, the invasive and migratory capabilities of NCM460, HT29, and HCT116 cells were reduced. Quantitative analysis of extracellular ATP post-treatment showed a significant elevation (P < 0.01). The C. albicans metabolite mixture had no effect on reactive oxygen species accumulation in CRC cells but led to a reduction in mitochondrial membrane potential, increased intracellular lipid peroxidation, and induced apoptosis. Metabolomic profiling revealed significant alterations, with 516 metabolites upregulated and 531 downregulated.

CONCLUSION

This study introduced a novel prognostic model for CRC risk assessment. The findings suggested that the C. albicans metabolite mixture exerted an inhibitory effect on CRC initiation.

Keywords: Candida albicans; Colorectal cancer; Metabolic characteristics; Extracellular ATP; Prognostic model

Core Tip: This study explored the paradoxical role of Candida albicans (C. albicans) in colorectal cancer (CRC), focusing on its tumor-modulating effects through metabolic interactions. A novel prognostic model incorporating five mRNA markers, EHD4, LIME1, GADD45B, TIMP1, and FDFT1, was developed, providing a framework for CRC risk assessment. The C. albicans metabolite mixture demonstrated a significant inhibitory effect on CRC initiation by reducing cell viability, altering gene expression, impairing migratory and invasive abilities, and promoting apoptosis without affecting reactive oxygen species accumulation. The study highlighted the potential of C. albicans metabolites as a therapeutic avenue in CRC management.