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

作　　者：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 

机构地区：[1]Department of Oncology,The First Affiliated Hospital of Xinxiang Medical University,Xinxiang 453000,Henan Province,China [2]Department of Biomedical Science,Universiti Sains Malaysia,Pinang 13200,Malaysia [3]Clinical College of Chinese Medicine,Gansu University of Chinese Medicine,Lanzhou 730000,Gansu Province,China [4]Department of Biomedical Sciences,Advanced Medical and Dental Institute,Universiti Sains Malaysia,Penang 13200,Malaysia [5]School of Public Health,Gansu University of Chinese Medicine,Lanzhou 730000,Gansu Province,China

出　　处：《World Journal of Clinical Oncology》2025年第4期195-279,共85页世界临床肿瘤学杂志(英文)

基　　金：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;Special Fund for Mentors of“Qihuang Talents”in the First-Level Discipline of Chinese Medicine,No.ZYXKBD-202415。

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.METHODSA prognostic model integrating C. albicans with CRC was developed, incorporating enrichment analysis, immuneinfiltration 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. Theprimary metabolite composition was characterized using liquid chromatography-mass spectrometry.RESULTSA prognostic model based on five specific mRNA markers, EHD4, LIME1, GADD45B, TIMP1, and FDFT1, wasestablished. The C. albicans metabolite mixture significantly reduced CRC cell viability. Post-treatment analysisrevealed a significant decrease in gene expression in HT29 cells, while the expression levels of TIMP1, EHD4, andGADD45B were significantly elevated in HCT116 cells. Conversely, LIME1 expression and that of other CRC celllines showed reductions. In normal colonic epithelial cells (NCM460), GADD45B, TIMP1, and FDFT1 expressionlevels were significantly increased, while LIME1 and EHD4 levels were markedly reduced. Following metabolitetreatment, the invasive and migratory capabilities of NCM460, HT29, and HCT116 cells were reduced. Quantitativeanalysis of extracellular ATP post-treatment showed a significant elevation (P < 0.01). The C. albicans metabolitemixture had no effect on reactive oxygen spec

关 键 词：Candida albicans Colorectal cancer Metabolic characteristics Extracellular ATP Prognostic model 

分 类 号：R73[医药卫生—肿瘤]