Abstract P76: Relative Expression of Transcripts Encoding Long and Short Isoforms of the PLAGL1 Zinc-Finger Protein Correlates with Progression and Prognosis in Colorectal Cancer: Evidence from Polish and TCGA Patient Cohorts

Background: PLAGL1 is a zinc-finger DNA-binding transcription factor with anti-proliferative properties. Genetic and epigenetic dysregulation of PLAGL1 has been implicated in the development and progression of various human cancers. The use of multiple alternative promoters and alternative splicing gives rise to numerous PLAGL1 transcript variants, resulting in two predominant protein isoforms: the longer isoform 2 and the shorter isoform 1. Alterations in the relative expression of PLAGL1 isoforms may represent a precise physiological regulatory mechanism that, when disrupted, could potentially contribute to various pathological processes. Our previous studies in the cohort of Polish patients with colorectal cancer (CRC) demonstrated decreased relative expression of PLAGL1 transcripts encoding isoform 2 in CRC tumors that correlated with the presence of distant metastases. Materials and Methods: In this study, we utilized data from The Cancer Genome Atlas (TCGA) cohort of CRC patients to (1) evaluate the prognostic significance of transcript variants encoding PLAGL1 isoforms, and (2) identify gene sets enriched in association with altered expression of PLAGL1 isoforms. Results: A reduced ratio of PLAGL1 isoform 2 to isoform 1 expression in CRC tumors was associated with advanced T-stage, perineural invasion, the presence of distant metastases, and worse prognosis. Bioinformatic analysis identified significant differences in gene set enrichment between CRC patients with low and high PLAGL1 isoform 2 to isoform 1 ratios. Conclusions: The results derived from TCGA datasets corroborate and extend our previous findings in the Polish cohort of CRC patients. Overall, these studies indicate that the relative expression of PLAGL1 isoforms may serve as a potential prognostic factor and therapeutic target in CRC. Acknowledgements: This research was funded by the Ministry of Science under “The Regional Initiative of Excellence Program” and the statutory grant of the School of Medicine, University of Warmia and Mazury in Olsztyn, Poland. Citation Format: Bartlomiej E. Krazinski, Anna E. Kowalczyk, Marzena Mogielnicka-Brzozowska, Jacek Kiezun, Janusz Godlewski. Relative Expression of Transcripts Encoding Long and Short Isoforms of the PLAGL1 Zinc-Finger Protein Correlates with Progression and Prognosis in Colorectal Cancer: Evidence from Polish and TCGA Patient Cohorts [abstract]. In: Proceedings of Frontiers in Cancer Science 2024; 2024 Nov 13-15; Singapore. Philadelphia (PA): AACR; Cancer Res 2025;85(15_Suppl):Abstract nr P76.