Construction and validation of a prognostic model based on metabolic characteristics of Candida albicans in colorectal cancer

Author:

Zhang HaoLing1,Zhang Haolong1,Chen Weifang2,Wang Yong3,Sapudin Siti Nurfatimah Mohd1,Sandai Doblin1,Harun Mohammad Syamsul Reza1,Zhang Zhongwen4,Wang Wei5,Song ZhiJing6,Fang Zhongxian2

Affiliation:

1. Department of Biomedical Sciences, Advanced Medical and Dental Institute, Universiti Sains Malaysia

2. Department of Hematology and Oncology, Putuo District People’s Hospital

3. Pathology Center, Gansu University of Chinese Medicine

4. School of Public Health, Gansu University of Chinese Medicine

5. College of Acupuncture-Moxibustion and Tuina, Gansu University of Chinese Medicine

6. Clinical College of Chinese Medicine, Gansu University of Chinese Medicine

Abstract

Abstract

There is evidence supporting the notion that Candida albicans (C. albicans) indeed contributes to human cancers. Interestingly, the efficacy of C. albicans in improving Colorectal cancer (CRC) has been confirmed. This study primarily explores the paradox of whether C. albicans promotes or inhibits the development of CRC, focusing on its metabolites mixture for relevant arguments. This study identified a total of 214 differentially expressed genes. A prognostic model containing 5 specific mRNA markers, namely EHD4, LIME1, GADD45B, TIMP1, and FDFT1, was constructed. C. albicans metabolites mixture reduced CRC cell activity. qRT-PCR results showed that compared to normal colonic epithelial cells, LIME and EHD4 were downregulated in CRC cells, while FDFT1 expression was significantly upregulated. Notably, the TIMP1 gene was significantly upregulated in HT29 cells, while it was significantly downregulated in HCT116 cells. Furthermore, post-intervention analysis showed a significant decrease in gene expression levels in HT29 cells, while the expression of TIMP1, EHD4, and GADD45B increased in HCT116 cells, with LIME and other CRC cells showing a corresponding decrease in expression. In NCM460 normal colonic epithelial cells, the expression levels of GADD45B, TIMP1, and FDFT1 genes were significantly upregulated, while the expression levels of LIME and EHD4 showed a significant downward trend. After metabolite intervention, the invasion and migration capabilities of NCM460 cells, HT29 cells, and HCT116 cells decreased. Additionally, quantitative measurement of eATP levels after intervention showed a significant increase (P < 0.01). This study's prognostic model opens up a new paradigm for prognostic assessment in CRC. The metabolites mixture of C. albicans play a protective role in the onset and progression of CRC, exhibiting dynamic interactions with cellular energetics.

Publisher

Research Square Platform LLC

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