Prognostic Significance of Cancer Stem Cell Markers and Tumor Microenvironment Components for Assessing the Efficacy of Chemoradiotherapy in Patients with Locally Advanced rectal cancer

Background: Despite the incorporation of neoadjuvant chemoradiotherapy into the standard treatment of locally advanced rectal cancer, significant variability in therapeutic response persists. This highlights the need for patient stratification using prognostic biomarkers. The identification of reliable morphological and immunohistochemical predictors of tumor resistance may enhance the effectiveness of personalized treatment strategies.
Objective: To assess the prognostic value of cancer stem cell markers and components of the tumor microenvironment in predicting response to chemoradiotherapy in patients with locally advanced rectal cancer.
Materials and Methods: The study included histological blocks obtained from biopsy and postoperative speciments of 75 patients with histoligically confirmed rectal adenocarcinoma who had undergone neoadjuvant chemoradiotherapy. Tumor regression grade (TRG) and immunohistochemical expression of ALDH1, TWIST, CD44, E-cadherin, LAG3, and CD20 were evaluated. Cut-off values were determined using ROC analysis. Associations between marker expression, clinicopathologic features, and treatment response were assessed. Results: A statistically significant association was found between poor response to chemoradiotherapy (TRG 2–3) and high expression of the following markers: ALDH1 >20% in 78.4% of patients (vs 26.3% in the TRG 0–1 group), TWIST >15% in 73.0% (vs 31.6%), CD44 >25% in 64.9% (vs 23.7%), LAG3 >10% in 64.9% (vs 28.9%), and CD20 >25% in 62.2% (vs 21.1%). Reduced E-cadherin expression (<30%) was observed in 62.2% of patients with TRG 2–3, compared to 23.7% in the marked morphological response group.
Conclusions: Assessment of the expression levels of the pathomorphological markers ALDH1, TWIST, CD44, E-cadherin, LAG3, and CD20 represents a significant prognostic indicator of tumor response to chemoradiotherapy. Integration of a comprehensive evaluation algorithm may facilitate personalize treatment strategies for patients with locally advanced rectal cancer.

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