Copyright
©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
Candida albicans and colorectal cancer: A paradoxical role revealed through metabolite profiling and prognostic modeling
Hao-Ling Zhang, Rui Zhao, Di Wang, Siti Nurfatimah Mohd Sapudin, Badrul Hisham Yahaya, Mohammad Syamsul Reza Harun, Zhong-Wen Zhang, Zhi-Jing Song, Yan-Ting Liu, Sandai Doblin, Ping Lu
Hao-Ling Zhang, Yan-Ting Liu, Ping Lu, Department of Oncology, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang 453000, Henan Province, China
Hao-Ling Zhang, Di Wang, Department of Biomedical Science, Universiti Sains Malaysia, Pinang 13200, Malaysia
Rui Zhao, Zhi-Jing Song, Clinical College of Chinese Medicine, Gansu University of Chinese Medicine, Lanzhou 730000, Gansu Province, China
Siti Nurfatimah Mohd Sapudin, Badrul Hisham Yahaya, Mohammad Syamsul Reza Harun, Sandai Doblin, Department of Biomedical Sciences, Advanced Medical and Dental Institute, Universiti Sains Malaysia, Penang 13200, Malaysia
Zhong-Wen Zhang, School of Public Health, Gansu University of Chinese Medicine, Lanzhou 730000, Gansu Province, China
Co-corresponding authors: Sandai Doblin and Lu Ping.
Author contributions: Zhang HL completed the first draft of the paper and finished the data processing; Zhao R, Wang D, Lok B, Mohd Sapudin SN, Yahaya BH, and Harun MSR completed the data check of the paper and provided suggestions for revision; Sandai D, Zhang ZW, Song ZJ, Liu YT, and Lu P revised the article.
Supported by Gansu Province Joint Fund General Program, No. 24JRRA878; Gansu Provincial Science and Technology Program Project, No. 24JRRA1020; Gansu Province Key Talent Program, No. 2025RCXM006; Teaching Research and Reform Program for Postgraduate Education at Gansu University of Traditional Chinese Medicine (GUSTCM), No. YBXM-202406; and Special Fund for Mentors of “Qihuang Talents” in the First-Level Discipline of Chinese Medicine, No. ZYXKBD-202415.
Institutional review board statement: This study was approved by Gansu University of Chinese Medicine and supported by Professor Zhijing Song from Gansu University of Chinese Medicine and Professor Ping Lu from the First Affiliated Hospital of Xinxiang Medical College.
Conflict-of-interest statement: The authors have no conflicts of interest to declare.
Data sharing statement: The data supporting the findings of this study are available from the corresponding author (or first author) upon reasonable request. Access to the data will be provided under appropriate conditions, ensuring that confidentiality and ethical standards are maintained.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
https://creativecommons.org/Licenses/by-nc/4.0/ Corresponding author: Ping Lu, Professor, Department of Oncology, The First Affiliated Hospital of Xinxiang Medical University Weihui, Xinxiang 453000, Henan Province, China.
lupingdoctor@163.com
Received: December 13, 2024
Revised: January 11, 2025
Accepted: January 23, 2025
Published online: April 24, 2025
Processing time: 104 Days and 2.2 Hours
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.
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.
