Lin Zhang1, Ming Fan1, Francesco Napolitano2, Xin Gao2, Ying Xu3,4,5, Lihua Li6. 1. Institute of Biomedical Engineering and Instrumentation, Hangzhou Dianzi University, Hangzhou, 310000, China. 2. Computer, Electrical and Mathematical Sciences and Engineering Division (CEMSE), Computational Bioscience Research Center (CBRC), King Abdullah University of Science and Technology (KAUST), Thuwal, 23955-6900, Saudi Arabia. 3. Cancer Systems Biology Center, The China-Japan Union Hospital, Jilin University, Changchun, 130033, China. 4. MOE Key Laboratory of Symbolic Computation and Knowledge Engineering, College of Computer Science and Technology, Jilin University, Changchun, 130012, China. 5. Computational Systems Biology Lab, Department of Biochemistry and Molecular Biology and Institute of Bioinformatics, University of Georgia, Athens, GA, 30602, USA. 6. Institute of Biomedical Engineering and Instrumentation, Hangzhou Dianzi University, Hangzhou, 310000, China. lilh@hdu.edu.cn.
Abstract
BACKGROUND: Metastasis is the most devastating stage of cancer progression and often shows a preference for specific organs. METHODS: To reveal the mechanisms underlying organ-specific metastasis, we systematically analyzed gene expression profiles for three common metastasis sites across all available primary origins. A rank-based method was used to detect differentially expressed genes between metastatic tumor tissues and corresponding control tissues. For each metastasis site, the common differentially expressed genes across all primary origins were identified as organ-specific metastasis genes. RESULTS: Pathways enriched by these genes reveal an interplay between the molecular characteristics of the cancer cells and those of the target organ. Specifically, the neuroactive ligand-receptor interaction pathway and HIF-1 signaling pathway were found to have prominent roles in adapting to the target organ environment in brain and liver metastases, respectively. Finally, the identified organ-specific metastasis genes and pathways were validated using a primary breast tumor dataset. Survival and cluster analysis showed that organ-specific metastasis genes and pathways tended to be expressed uniquely by a subgroup of patients having metastasis to the target organ, and were associated with the clinical outcome. CONCLUSIONS: Elucidating the genes and pathways underlying organ-specific metastasis may help to identify drug targets and develop treatment strategies to benefit patients.
BACKGROUND: Metastasis is the most devastating stage of cancer progression and often shows a preference for specific organs. METHODS: To reveal the mechanisms underlying organ-specific metastasis, we systematically analyzed gene expression profiles for three common metastasis sites across all available primary origins. A rank-based method was used to detect differentially expressed genes between metastatic tumor tissues and corresponding control tissues. For each metastasis site, the common differentially expressed genes across all primary origins were identified as organ-specific metastasis genes. RESULTS: Pathways enriched by these genes reveal an interplay between the molecular characteristics of the cancer cells and those of the target organ. Specifically, the neuroactive ligand-receptor interaction pathway and HIF-1 signaling pathway were found to have prominent roles in adapting to the target organ environment in brain and liver metastases, respectively. Finally, the identified organ-specific metastasis genes and pathways were validated using a primary breast tumor dataset. Survival and cluster analysis showed that organ-specific metastasis genes and pathways tended to be expressed uniquely by a subgroup of patients having metastasis to the target organ, and were associated with the clinical outcome. CONCLUSIONS: Elucidating the genes and pathways underlying organ-specific metastasis may help to identify drug targets and develop treatment strategies to benefit patients.