title: Characterization of cytokinome landscape for clinical responses in human cancers.
abstract: Dysfunctional intratumoral immune reactions are shaped by complex networks of cytokines (including chemokines), and how the cytokinome landscape coordinates with tumors has not been systematically investigated. Using high-dimensional datasets of cancer specimens, we explored the transcript abundance, biomarker potential, and prognostic impact of local cytokines across 19 tumor types. We found that most cytokines are highly locally dysregulated (p= 0.024), revealing spatiotemporal pattern of local cytokines in the development of cancers. In addition, we noted the significant downregulation ofCCL14andCXCL12in 9 and 10 cancer types, respectively, implying their crucial roles in tumor pathogenesis. We also found that cytokines showed significantly higher specificity properties compared to other protein-coding genes (PCGs) in primary tumor specimens (p<< 0.001), indicating that tissue context remains an issue when considering cancer cytokinomes. Finally, we linked concentrations of local cytokines to patient survival. Our results thus provide a panoramic view of pan-cancer cytokinomes, which highlights tumor type specificity of cancer-related cytokines and their impacts on disease prognosis.
authors.affiliation: Department of Clinical Pharmacy, School of Pharmacy, Taipei Medical University, Taipei, Taiwan; Master Program for Clinical Pharmacogenomics and Pharmacoproteomics, School of Pharmacy, Taipei Medical University, Taipei, Taiwan.
authors.forename: Henry Sung-Ching
authors.initials: HS
authors.lastname: Wong
authors.affiliation: Department of Clinical Pharmacy, School of Pharmacy, Taipei Medical University , Taipei, Taiwan.
authors.forename: Che-Mai
authors.initials: CM
authors.lastname: Chang
authors.affiliation: Institute for Molecular Engineering, University of Chicago , Chicago, IL, USA.
authors.forename: Xiao
authors.initials: X
authors.lastname: Liu
authors.affiliation: Institute of Cellular and Organismic Biology, Academia Sinica, Taipei, Taiwan; Department of Pharmacy, Taipei Medical University-Shuang Ho Hospital, Taipei, Taiwan.
authors.forename: Wan-Chen
authors.initials: WC
authors.lastname: Huang
authors.affiliation: Department of Clinical Pharmacy, School of Pharmacy, Taipei Medical University, Taipei, Taiwan; Master Program for Clinical Pharmacogenomics and Pharmacoproteomics, School of Pharmacy, Taipei Medical University, Taipei, Taiwan; Center for Biomarkers and Biotech Drugs, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Pharmacy, Taipei Medical University-Wan Fang Hospital, Taipei, Taiwan.
authors.forename: Wei-Chiao
authors.initials: WC
authors.lastname: Chang
keywords: Cytokinome landscape; cytokines and chemokines; drug-target enrichment; pan-cancer analysis; survival analysis; transcription profiles