文献类型：期刊文献

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

作者：Zhang, Hao-Ling[1,2];Zhao, Rui[3];Wang, Di[2];Sapudin, Siti Nurfatimah Mohd[4];Yahaya, Badrul Hisham[4];Harun, Mohammad Syamsul Reza[4];Zhang, Zhong-Wen[5];Song, Zhi-Jing[3];Liu, Yan-Ting[1];Doblin, Sandai[4];Lu, Ping[1]

第一作者：Zhang, Hao-Ling

通信作者：Lu, P[1]

机构：[1]Xinxiang Med Univ, Affiliated Hosp 1, Dept Oncol, Xinxiang 453000, Henan, Peoples R China;[2]Univ Sains Malaysia, Dept Biomed Sci, George Town 13200, Malaysia;[3]Gansu Univ Chinese Med, Clin Coll Chinese Med, Lanzhou 730000, Gansu, Peoples R China;[4]Univ Sains Malaysia, Adv Med & Dent Inst, Dept Biomed Sci, George Town 13200, Malaysia;[5]Gansu Univ Chinese Med, Sch Publ Hlth, Lanzhou 730000, Gansu, Peoples R China

第一机构：Xinxiang Med Univ, Affiliated Hosp 1, Dept Oncol, Xinxiang 453000, Henan, Peoples R China

通信机构：[1]corresponding author), Xinxiang Med Univ, Affiliated Hosp 1, Dept Oncol, Xinxiang 453000, Henan, Peoples R China.

年份：2025

卷号：16

期号：4

外文期刊名：WORLD JOURNAL OF CLINICAL ONCOLOGY

收录：WOS:【ESCI(收录号:WOS:001478350500020)】；

语种：英文

外文关键词：Candida albicans; Colorectal cancer; Metabolic characteristics; Extracellular ATP; Prognostic model

摘要：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.