Abstract 3573: Identification and functional characterization of prognostic long non coding RNA LADDER in lung cancer
Authors: Sathiya Pandi Narayanan, Sudhanshu Shukla, Jean Tien, Palak Shah, Sunita Shankar, Sethuramasundaram Pitchaiya, Srihari Srinivasan, Yuping Zhang, Xiaoming Wang, Lanbo Xiao, Xuhong Cao, Susan Freier, Andrew Watt, Shuling Guo, Felix Feng, David Beer, Saravana M. Dhanasekaran, Arul M. Chinnaiyan
Journal: Cancer Research (2019)

Abstract Non-small cell lung cancer (NSCLC) is a leading cause of cancer-related deaths in the world. Disease subtypes include lung adenocarcinoma (LUAD), which accounts for nearly 50% of lung malignancies, and lung squamous carcinoma (LUSC). Disease diagnosis at late stages and limited therapeutic options are the major causes for the poor prognosis of lung cancer patients. Additionally, lack of discriminatory diagnostic and prognostic biomarkers have hampered therapeutic management and, consequently, NSCLC patients are treated as one entity. In this modern era, the development of next generation based RNA sequencing (RNA-Seq) methodologies enable us to accurately quantify the transcriptional abundance in cells in a highly reproducible and reliable manner. By utilizing this technology, we sequenced a large cohort of lung cancer samples and leveraged several publically available RNA-Seq datasets for analysis to facilitate a deeper understanding of the disease. Furthermore, from the large RNA-Seq datasets, we also discovered long noncoding RNAs (lncRNA). These transcripts, which are longer than 200 nucleotides that are not translated into protein, have tissue-, lineage-, and cancer-specific expression patterns. In our previous study, we developed a highly significant prognostic marker gene signature by analyzing 255 LUAD patients from The Cancer Genome Atlas (TCGA) dataset. Using a training cohort, 96 genes including 5 lncRNAs had significant prognostic associations with lung cancer. Further, a stepwise regression model identified a four-gene signature, including one lncRNA (LADDER). The four-gene signature was then validated in two independent patient cohorts from the TCGA and in-house data. Functional studies showed that inhibition of LADDER lncRNA using both siRNA and ASOs decreased cell proliferation in lung cancer cells. In addition, knockdown of LADDER lncRNA using ASOs decreased lung cancer cell growth in vivo. Taken together, we have identified the lncRNA LADDER, a member of a four-gene prognostic signature, to play a functional role in lung cancer progression as well as serve as a robust prognostic marker. Note: This abstract was not presented at the meeting. Citation Format: Sathiya Pandi Narayanan, Sudhanshu Shukla, Jean Tien, Palak Shah, Sunita Shankar, Sethuramasundaram Pitchaiya, Srihari Srinivasan, Yuping Zhang, Xiaoming Wang, Lanbo Xiao, Xuhong Cao, Susan Freier, Andrew Watt, Shuling Guo, Felix Feng, David Beer, Saravana M. Dhanasekaran, Arul M. Chinnaiyan. Identification and functional characterization of prognostic long non coding RNA LADDER in lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3573.