Abstract 2771: Identification of novel genes associated with metastasis from TCGA transcriptomic data

Abstract

Abstract Introduction: Many cancer patients suffer from metastasis in bone, brain, liver and lung. However, understanding of metastasis in molecular level is quite limited. To improve survival rate and quality of life, preventing metastasis is crucial. In this study, we analyzed transcriptomic data with tumor node metastasis (TNM) classification from The Cancer Genome Atlas (TCGA) to identify genes associated with metastasis. Method: TCGA samples in 20 solid tumor types with both transcriptome and TNM annotation data are used. To obtain the best cut point separating cohorts of high and low gene expression, Hothorn and Lausen’s method is used. A contingency table is created with expression separated by the the cut point and presence of staging T, N, M for each gene. Association between the staging category and the gene was calculated with Fisher’s exact test. Results: In total, 13,220 distinct genes including miRNAs are associated with either lymph node or distant metastasis for some cancer types with a loose criteria of p-value < 1.0e-3. Among them, we identified 1,357 genes with p-value < 1.0e-8. ADAMTS12, AURKB, BUB1, C17orf53, CCNA2, CEP55, EPR1, KIF4A, KIF11, KRT80, MELK, MKI67, NCAPG, NEIL3, PBK, PLK1, RRM2, TPX2, miR139, miR30a, miR375, and miR379 appear most commonly in lymph node metastasis for many cancer types. Likewise, NOP56, PKD1L2, miR150, miR365, miR9, miR149, miR210, miR425, miR675, and miR937 are most commonly associated genes in distant metastasis. Many of these genes have been already reported in association with metastasis. Conclusions: This study created comprehensive list of metastasis associated genes for the 20 solid tumors in TCGA. They would be useful as diagnostic and prognostic biomarkers; however, we found therapeutically relevant genes such as PLK1, AURKB, MET, MELK, CDK1, BUB1, and PBK. Some adhesion molecules associated with a particular cancer type might explain its organ destination preference. Among distant metastatic miRNAs discovered, metastasis promoting miRNAs in high abundance might be engaged in homing as exosomal miRNAs by reprogramming destination niche in favor of migrating tumor cells. Further work to reveal metastasis mechanism and to discover some pharmaceutical agents to prevent metastasis will be conducted. Citation Format: Takahiko Koyama, Laxmi Parida. Identification of novel genes associated with metastasis from TCGA transcriptomic data [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 2771.