Intratumoral fungal burden of <i>Candida tropicalis</i> as a novel prognostic biomarker for recurrence and mortality in colorectal cancer

BACKGROUND: The crucial role of gut fungus dysbiosis in the carcinogenesis and progression of colorectal cancer (CRC) has recently garnered increasing attention. In this study, the potential role of Candida tropicalis, commensal gut fungi, in predicting CRC prognosis was investigated. METHODS: A total of 304 frozen surgical cancer tissue specimens were obtained from patients with CRC and evaluated the intratumoral C. tropicalis burden using quantitative polymerase chain reaction assays. Mycobial composition and diversity analyses were performed by analyzing publicly available metagenomic datasets. RESULTS: Metagenomic dataset analysis revealed significant differences in fungal composition and diversity of Candida species among adjacent normal and CRC tissues. The 5-year recurrence-free survival and disease-specific survival rates were significantly worse in patients with a high intratumoral C. tropicalis burden than in those with a low burden (78.0% vs. 86.6%; p = .03 and 88.9% vs. 98.0%; p < .01, respectively). Furthermore, multivariate Cox regression analysis revealed that increased intratumoral C. tropicalis burden was a significant independent predictor for recurrence-free survival (hazard ratio [HR]: 1.92; 95% CI, 1.08-3.44; p = .03) and disease-specific survival (HR: 4.29; 95% CI, 1.36-13.5; p = .03). CONCLUSIONS: These results have demonstrated, possibly for the first time, the potential of intratumoral C. tropicalis burden as a novel prognostic biomarker for recurrence and mortality in patients with CRC.