Autofluorescent Cancer Stem Cells: Potential Biomarker to Predict Recurrence in Resected Colorectal Tumor.

ABSTRACT

Cancer stem cells (CSCs) in colorectal cancer (CRC) drive intratumoral heterogeneity and distant metastases. Previous research from our group showed that CSCs can be easily detected by autofluorescence (AF). The aim of the present study was to evaluate the potential role of AF CSCs as a prognostic biomarker for CRC relapse. Seventy-five freshly-resected tumors were analyzed, by flow cytometry. AF was categorized as high (H-AF) or low (L-AF), and results were correlated with histological features (grade of differentiation, presence of metastases in lymph nodes (LN), perivascular and lymphovascular invasion) and clinical variables (time to relapse and overall survival). Nineteen out of 75 (25.3%) patients experienced relapse (local or distant), 13 out of these 19 patients showed positive LNs and 6 patients had H-AF. Of note, 4 of them died before 5 years. While patients with H-AF CSCs percentages in the global population experienced 1.5 times increased relapse -HR 1.47, CI 95% (0.60 - 3.63), patients with H-AF CSC percentages and LN metastases had the highest risk of relapse; HR 7.92, p< 0.004, CI 95% (1.97 - 31.82). These data support AF as an accurate and feasible marker to identify CSCs in resected CRC. A strong statistical association between H-AF CSCs and the risk of relapse was observed, particularly in patients with positive LNs, suggesting that H-AF patients might benefit from adjuvant chemotherapy regimens and intensive surveillance due to their high propensity to experience disease recurrence.