Autophagy Dysregulation in Crohn’s Disease and Colorectal Cancer—An Analysis of <em>BECN1</em>, <em>PINK1</em>, and <em>LAMP2 </em>Gene Expression

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Abstract

Crohn’s disease (CD) and colorectal cancer (CRC) are clinically distinct but pathogenetically related conditions in which significant abnormalities in autophagy are observed. The aim of the study was to evaluate the expression of three key autophagy-related genes, i.e., BECN1 (macroautophagy), PINK1 (mitophagy) and LAMP2 (chaperone-mediated autophagy) in tissue samples from patients with CD and CRC. The study material included samples from 48 patients with CD (n = 96 biopsy samples) and 87 patients with CRC (n = 87 tumors; n = 87 normal paired controls). Transcriptomic analyses were performed using Affymetrix HG-U133A microarrays. They were confirmed by RT-qPCR. The Kruskal-Wallis test with Dunn’s post hoc analysis (α = 0.05) and Spearman’s correlation coefficients were used for statistical evaluation. Expression of BECN1 and LAMP2 was significantly decreased in both CD and CRC compared to the controls (p = 0.009; p = 0.023, respectively). However, PINK1 showed significantly higher expression levels in CD compared to CRC and the controls (p &lt; 0.001). The clinical stages of CRC (I-IV) did not significantly affect the expression of the analyzed genes. The study findings confirm the presence of common abnormalities in autophagy in CD and CRC with decreased macroautophagy and chaperone-mediated autophagy with the compensatory activation of mitophagy. BECN1, PINK1 and LAMP2 expressions may have a diagnostic and therapeutic value in the context of chronic inflammation and colorectal carcinogenesis.

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