Abstract 3372: Comprehensive analysis of estrogen-regulated testis specific lncRNAs in breast cancer
Authors: Ramos Enrique I. , Yang Barbara , Choudhari Ramesh , Sedano Melina J. , Gadad Shrikanth S. 
Published: June 2022

Long non-coding RNAs (lncRNAs) have transcripts longer than 200 nucleotides and recent studies have established they are abnormally expressed in cancer and have the potential to function as either oncogenes or tumor suppressors; Therefore, their potential utility as biomarkers and targets for different types cancer. Breast cancer is the most common cancer diagnosed (excluding skin cancers) among women in the United States, accounting for nearly 1 in 3 cancers. Thus, the need for effective targets and biomarkers to prevent/treat this disease.

Available datasets to study gene expression in human diseases are a valuable asset to better understand complex disorders and phenotypes. In this study, we are using three publicly available datasets: The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx) and Cancer Cell Line Encyclopedia (CCLE) to study breast cancer and identify coding and lncRNA transcripts differentially expressed in tumors and highly specific to testis. At the end of our analysis pipeline, we identified a total of 1,668 upregulated genes in breast cancer and 1,163 downregulated genes in breast cancer, from which a total of 31 were lncRNAs. Characterization of the lncRNAs show highly specificity in diverse types of breast cancer (Basal, Luminal A, Luminal B and HER2) compared to protein coding genes. Cell line analysis of breast cancer RNA-Seq samples by the CCLE- Broad Institute show clustering of gene expression for the identified lncRNAs according to molecular subtype. Moreover, categorization of the lncRNAs using TCGA is described by ER- and ER+ status, molecular subtype, comparison between breast tumor, breast normal and GTEx breast, and gene ontology analysis of KEGG Pathways using DAVID. Furthermore, Kaplan-Meier analysis is shown to estimate the potential survival outcome of patients with high/low expression of lncRNAs in breast cancer. Lastly, we compared results from qRT-PCR with our in-silico data for the top lncRNAs and findings show a good correlation between both platforms.

Overall, we identify a total of 31 lncRNAs that are estrogen-regulated testis specific in breast cancer by differential expression analysis. In addition, we provide a full genomic characterization of the lncRNAs that show expression according to different molecular subtypes using data from TCGA, GTEx and CCLE. Finally, we show potential survival outcome of high/low expression of identified lncRNAs in breast cancer patients. Taken together, we present lncRNAs specific in breast cancer and high expression in testis, along with their comprehensive characterization of expression signatures. Further studies, are needed to assess their efficacy as potential biomarkers and therapeutic targets in breast cancer.

S.S.G. is supported by a grant from the Cancer Prevention and Research Institute of Texas (CPRIT; RR170020). S.S.G. is also supported by a grant from Lizanell and Colbert Coldwell foundation.

Citation Format: Enrique I. Ramos, Barbara Yang, Ramesh Choudhari, Melina J. Sedano, Shrikanth S. Gadad. Comprehensive analysis of estrogen-regulated testis specific lncRNAs in breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3372.