Effect of aberrant fructose metabolism following SARS-CoV-2 infection on colorectal cancer patients' poor prognosis

PLoS Comput Biol. 2024 Sep 27;20(9):e1012412. doi: 10.1371/journal.pcbi.1012412. eCollection 2024 Sep.

Abstract

Most COVID-19 patients have a positive prognosis, but patients with additional underlying diseases are more likely to have severe illness and increased fatality rates. Numerous studies indicate that cancer patients are more prone to contract SARS-CoV-2 and develop severe COVID-19 or even dying. In the recent transcriptome investigations, it is demonstrated that the fructose metabolism is altered in patients with SARS-CoV-2 infection. However, cancer cells can use fructose as an extra source of energy for growth and metastasis. Furthermore, enhanced living conditions have resulted in a notable rise in fructose consumption in individuals' daily dietary habits. We therefore hypothesize that the poor prognosis of cancer patients caused by SARS-CoV-2 may therefore be mediated through fructose metabolism. Using CRC cases from four distinct cohorts, we built and validated a predictive model based on SARS-CoV-2 producing fructose metabolic anomalies by coupling Cox univariate regression and lasso regression feature selection algorithms to identify hallmark genes in colorectal cancer. We also developed a composite prognostic nomogram to improve clinical practice by integrating the characteristics of aberrant fructose metabolism produced by this novel coronavirus with age and tumor stage. To obtain the genes with the greatest potential prognostic values, LASSO regression analysis was performed, In the TCGA training cohort, patients were randomly separated into training and validation sets in the ratio of 4: 1, and the best risk score value for each sample was acquired by lasso regression analysis for further analysis, and the fifteen genes CLEC4A, FDFT1, CTNNB1, GPI, PMM2, PTPRD, IL7, ALDH3B1, AASS, AOC3, SEPINE1, PFKFB1, FTCD, TIMP1 and GATM were finally selected. In order to validate the model's accuracy, ROC curve analysis was performed on an external dataset, and the results indicated that the model had a high predictive power for the prognosis prediction of patients. Our study provides a theoretical foundation for the future targeted regulation of fructose metabolism in colorectal cancer patients, while simultaneously optimizing dietary guidance and therapeutic care for colorectal cancer patients in the context of the COVID-19 pandemic.

MeSH terms

  • COVID-19* / metabolism
  • Colorectal Neoplasms* / genetics
  • Colorectal Neoplasms* / metabolism
  • Colorectal Neoplasms* / virology
  • Computational Biology / methods
  • Female
  • Fructose* / metabolism
  • Humans
  • Male
  • Nomograms
  • Prognosis
  • SARS-CoV-2*

Substances

  • Fructose

Grants and funding

This work was partly supported by National Natural Science Foundation of China (81602510 to JY), High-Quality Development Project at China Medical University, supported by the Liaoning Provincial Department of Science and Technology (2023JH2/20200100 to JY) and National Natural Science Foundation of China (82370506). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.