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We thank the patients that participated in this study. This study was supported by a Ramon y Cajal Merit Award (RYC-2012-12104) from the Ministerio de Economia y Competitividad, Spain (B. Sainz); a Coordinated grant (GC16173694BARB) from the Fundacion Asociacion Espanola Contra el Cancer (B. Sainz); FIS grants PI15/01507 and PI18/00757 (B. Sainz; cofinanced through Fondo Europeo de Desarrollo Regional "Una manera de hacer Europa"); and, in part, by the Programme S2018/BAA-4343 ALIBIRD2020-CM (E. Casado) "Precision nutrition therapeutic formulas for cancer" in the framework of the call for applications for technological aid 2018 for the implementation of R&D Programmes of the Community of Madrid, with 50% cofunding from the European Social Fund.

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

Publicated to:Cancer Research Communications. 4 (10): 2575-2588 - 2024-10-01 4(10), DOI: 10.1158/2767-9764.CRC-24-0188

Authors: Alcala, Sonia; San Martin, Gonzalo Serralta; Moreno-Rubio, Juan; Salinas, Silvia; Lopez-Gil, Juan Carlos; Rojo Lopez, Jose Alberto; Martinez Alegre, Javier; Cortes Bandy, David Abraham; Zambrana, Francisco; Jimenez-Gordo, Ana-Maria; Casado, Enrique; Lopez-Gomez, Miriam; Sainz, Bruno

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Abstract

Cancer stem cells (CSC) in colorectal cancer 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 colorectal cancer relapse. Seventy-five freshly resected tumors were analyzed by flow cytometry. AF was categorized as high (H-AF) or low, and the results were correlated with histologic 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 of the 75 (25.3%) patients experienced relapse (local or distant); of these 19 patients, 13 showed positive LNs and 6 had H-AF. Of note, four of them died before 5 years. Although patients with H-AF CSC percentages in the global population experienced 1.5 times increased relapse [HR, 1.47; 95% confidence interval (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; 95% confidence interval (1.97-31.82)]. These data support AF as an accurate and feasible marker to identify CSCs in resected colorectal cancer. 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. Significance: AF has been proven to be an accurate biomarker for CSC identification; however, to date, their role as a prognostic factor after resection of colorectal cancer tumors has not been investigated. Our results show that determining the presence of AF CSCs after tumor resection has prognostic value and represents a potentially important tool for the management of patients with colorectal cancer.

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