Clinical importance of LEDGF/p75 in colorectal cancer prognosis

Introduction Colorectal cancer ranks third in men and second in women, with 153,020 new cases and 52,550 deaths in 2023. While predominantly affecting those over 65 years, 13% occur in individuals under 50 years. Biomarker analysis, including APC, BRAF, KRAS, and TP53, aids early detection, but rising incidence due to lifestyle changes projects 2.2 million new cases by 2030. Early screening is crucial for optimizing treatment outcomes and disease monitoring in colorectal cancer, as it enables the identification and intervention of malignancy at an early stage, thereby improving survival rates and reducing the need for invasive procedures - this process is significantly augmented by the use of early biomarkers. Methods This study analyzed the expression of the stress oncoprotein LEDGF/p75 and the ubiquitin E2 conjugating enzyme UBC13 in 15 colorectal cancer tissue samples and adjacent non-tumor tissues, obtained from the same patients. Western blot analysis was used, and results were further validated using mRNA expression data from 521 patients in the TCGA database. Results LEDGF/p75 expression was significantly elevated in nearly all tumor tissue samples compared to adjacent tissue (11 / 15, 73.3 %). Additionally, enzyme UBC13, a key regulator in the degradation of signaling molecules, was also increased in most tumor tissue samples (9 / 15, 60.0 %). Co-overexpression of LEDGF/p75 and UBC13 was evident in 6 / 6 patients. Conclusion This study confirms the upregulation of LEDGF/p75 in colorectal cancer and shows its correlation with KRAS and MSH2 mutations. The role of LEDGF/p75 in genomic instability and interactions with DNA repair proteins may contribute to drug resistance and increased tumor aggressiveness. LEDGF/p75’s potential as a prognostic biomarker independent of lymph node involvement or CEA levels highlights its potential in personalized therapy and warrants further research into its therapeutic targeting.