Abstract
Ultraconserved regions (UCRs) are 481 genome segments, with length longer than 200 bp, that are 100% conserved among humans, mice, and rats. The majority of UCRs are transcriptionally active (T-UCRs) as many of them produce non-coding RNAs. In a previous study, we evaluated the expression level of T-UCRs in breast cancer (BC) patients and found that 63% of transcripts correlated with some clinical and/or molecular parameter of BC. In this study, we delved into the expression levels of 12 T-UCRs and correlated them with clinicopathological parameters, immunohistochemical markers, and overall survival in two breast cancer cohorts: TCGA and Brazilian patients. We found that uc.268 is more expressed in TCGA patients under 40 years of age, associated with progesterone receptor (PR) and estrogen receptor (ER), and its high expression is found in luminal A. Lower uc.84 and uc.376 were respectively observed in metastatic and stage IV tumors associated with good prognostic in luminal B. Moreover, uc.84 was only related to the HER2+, while uc.376 was related to ER+ and PR+, and HER2+. A panel composed of uc.147, uc.271, and uc.427 distinguished luminal A from triple negative patients with an AUC of 0.9531 (sensitivity 92.19% and specificity 86.76%). These results highlight the potential role of T-UCRs in BC and provide insights into the potential application of T-UCRs as biomarkers.
Highlights
Human genome sequencing demonstrated that only 2% of DNA are protein-coding genes
The T-Ultraconserved regions (UCRs) uc.138, uc.311, uc.376, and uc.456 were down expressed while uc.147, uc.193, uc.268, uc.271, uc.378, and uc.427 were highly expressed in the tumor samples
The diagnostic potential of transcribed ultraconserved regions (T-UCRs) was analysed through receiver operating characteristic (ROC) curves (Figure 2)
Summary
Human genome sequencing demonstrated that only 2% of DNA are protein-coding genes. The remaining 98% constitutes what was previously called the “dark matter” of molecular biology and includes hidden information mainly responsible for phenotype regulation. It is proven that this region can be transcribed into distinct RNAs that have an impact on gene regulation [2]. Those RNAs were named non-coding RNAs (ncRNAs), which include a variety of molecules and are subdivided into two major groups: miRNAs 200 bp) and long non-coding RNA (with a sequence of more than 200 bp) [3]. Ultraconserved regions (UCRs) are regions of conserved DNA segments, which have
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
