Transcribed Ultraconserved Regions Are Associated with Clinicopathological Features in Breast Cancer

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.

Transcribed-Ultra Conserved Regions (T-UCRs) a New Light on a Dark Matter

“…One is for distinguishing Barrett's esophagus from the squamous epithelium and another is for evaluating progression from normal to adenocarcinoma. Zambalde et al presented two panels of T-UCRs as diagnostic biomarkers for breast cancer and a third panel that distinguished with high sensitivity and specificity luminal A from triplenegative patients [87]. Finally, we come to studies such as that by Ciaramella et al in which the authors propose a new biomarker panel of T-UCRs using machine learning techniques [97].…”

A first comprehensive analysis of Transcribed Ultra Conserved Regions uncovers important regulatory functions of novel non-coding transcripts in gliomas.

“…Because of their ultra-conservation and their deregulation, it is believed that TUCRs may have important regulatory roles in cancer. [2][3][4][5][6][7][8][9][10][11] About 90% of the genome is transcribed, but only ~2 percent of the transcriptome is translated. The remainder of the transcriptome is made up of non-coding elements that serve key regulatory roles.…”

Transcribed Ultraconserved Regions: New regulators in cancer signaling and potential biomarkers

“…The association of 12 T-UCRs with clinical features was also analyzed in depth ( Zambalde et al, 2022 ). Uc.84 was related to the HER2+ and low expression found in metastatic tumors, while Uc.376 was associated with ER+, PR+, and HER2+.…”

“…The potential utility of T-UCRs as biomarkers was suggested. For example, a panel with Uc.147, Uc.271, and Uc.427 distinguished luminal A from triple-negative patients with an Area Under the Curve (AUC) of 0.95 ( Zambalde et al ., 2022 ).…”