Integrated Bioinformatic and Experimental Analysis of SLFN11 Expression and Clinical Significance in Locally Advanced Rectal Cancer

Background/Objectives: Schlafen 11 (SLFN11) encodes a DNA damage response protein implicated in sensitivity to DNA-damaging therapies and has been proposed as a predictive biomarker in several malignancies. This study aimed to characterize SLFN11 expression and evaluate its prognostic and predictive significance in locally advanced rectal cancer (LARC). Methods: Publicly available datasets were interrogated using UCSC Xena, GEPIA2, TNMplot, KMplot, ROC Plotter, and GEO databases. SLFN11 expression was assessed by quantitative real-time PCR in paired tumor and adjacent non-tumor tissues collected before and after neoadjuvant chemoradiotherapy (nCRT) from 26 patients with LARC. Associations with clinicopathological characteristics, pathological response, and survival outcomes were analyzed. Results: Publicly available datasets demonstrated lower SLFN11 expression in rectal tumor tissues compared with non-tumor tissues. In our cohort, no significant differences in SLFN11 expression were observed between paired tumor and adjacent non-tumor tissues either before or after nCRT. However, SLFN11 expression increased significantly following nCRT in both tissue types. Nevertheless, neither bioinformatic analyses nor our cohort demonstrated a significant association between SLFN11 expression and survival outcomes. Likewise, no significant predictive value of SLFN11 expression for response to nCRT was observed in ROC Plotter analysis, most GEO datasets, or our clinical cohort. The prognostic and predictive findings should be considered exploratory due to limited statistical power. Conclusions: Although SLFN11 expression is reduced in rectal tumor tissues and appears to be influenced by nCRT, its prognostic and predictive value in LARC remains uncertain. Larger studies are warranted to clarify its biological and clinical significance.