Abstract 3681: Transcribed ultraconserved regions are associated with survival in multiple tumor types

Abstract

Abstract Ultraconserved regions (UCRs), encompassing 481 genomic segments identical across humans, mice, and rats, and conserved in other species, are distributed across all human chromosomes except 21 and Y. Over 90% of these regions, termed transcribed ultraconserved regions (T-UCRs) are expressed in at least one human tissue. Although extensively studied in the context of cancer since their discovery, the prognostic significance of T-UCRs in a pan-cancer context has not been explored. For this, TCGA data extracted from the TANRIC platform was utilized, differential expression and survival analysis was performed on different tumor types. Our analysis revealed that approximately 300 UCRs were expressed in the majority of the 20 tumor tissues. Additionally, it was noted that all examined tumor tissues expressed a higher number of UCRs compared to their non-tumor counterparts. Through t-distributed stochastic neighbor embedding (t-SNE) analysis, UCR expression patterns could distinguish primary tumor origins and types. Regarding the prognostic value, we identified 100 (20,8%) T-UCRs associated with disease-specific survival (DSS) and 102 (21.2%) T-UCRs associated with progression-free interval (PFI). Those T-UCRs are particularly important in the survival outcomes of kidney renal clear cell carcinoma (KIRC) and low-grade gliomas (LGC). In addition, we verified that uc.44, uc.48, uc.135, uc.144, uc.153, uc.217, uc.255, uc.256, uc.344, uc.357, uc.390, uc.427 and uc.436 were associated with survival of more than one tumor. Particularly, uc.135 high expression was associated with poor prognosis in Kidney Renal Papillary Cell Carcinoma (KIRP) and LGC, and good prognosis in KIRC. Uc.135 are mapped on MECOM gene, coding an oncoprotein acting as transcriptional regulator and involved in apoptosis, proliferation, and cell differentiation. Our findings suggest that analysis of T-UCRs expression have the potential to be used as predictive biomarkers and can help in studying the mechanisms and specific roles of the highlighted T-UCRs in cancer. Citation Format: Ana Carolina Rodrigues, Douglas Adamoski, Daniela F. Gradia, Jaqueline Carvalho de Oliveira. Transcribed ultraconserved regions are associated with survival in multiple tumor types [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3681.