Abstract 174: In-depth transcriptomic comparisons provide novel insights into cancer metastasis

Abstract

Abstract Comparison of the transcriptome between primary and metastatic cancer is frequently performed to study cancer metastasis; however, distilling plausible biology from the comparison results remains a big challenge. We show that in the differential expression (DE) analysis performed on bulk RNAseq data a large proportion of DE genes are identified due to technical issues instead of biological differences between primary and metastatic cancer cells. Next, we develop a computational pipeline DEBoost to minimize such artifacts and apply it to five cancer types. We perform comprehensive analysis on the retained tumor-intrinsic DE genes to explore the biological mechanisms underlying the metastasis of different cancer types. Many of the DE genes are associated with the progression of primary cancer, suggesting the differential expression may have already been established before metastasis. Clustering analysis on DE genes identifies CNVs that account for the transcriptomic change and we further confirm 19p13.12 amplification drives the metastasis of primary Basal-like breast cancer via activating NOTCH signaling pathway. We also find that cell cycling is more active in metastatic prostate cancer than in primary cancer, suggesting the difference of responses to treatment like cell cycling inhibitors. Finally, we show that some metastatic cancer cells tend to express genes whose expression is normally observed at the metastasis site and we experimentally validate this phenomenon in colorectal cancer liver metastasis. Our pan-cancer liver metastasis study provides novel biological insights into cancer metastasis and meanwhile demonstrates the feasibility of characterizing tumor-intrinsic DE genes in cancer metastasis using our computational pipeline. Citation Format: KE LIU, Benjamin S. Glicksberg, Shreya Paithankar, Bin Chen. In-depth transcriptomic comparisons provide novel insights into cancer metastasis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 174.