Ann. N.Y. Acad. Sci. ISSN 0077-8923 ANNALS OF THE NEW YORK ACADEMY OF SCIENCES Issue: Glycobiology of the Immune Response Integrated approach toward the discovery of glyco-biomarkers of inﬂammation-related diseases Takashi Angata, Reiko Fujinawa, Ayako Kurimoto, Kazuki Nakajima, Masaki Kato, Shinji Takamatsu, Hiroaki Korekane, Cong-Xiao Gao, Kazuaki Ohtsubo, Shinobu Kitazume, and Naoyuki Taniguchi Systems Glycobiology Research Group, Chemical Biology Department, RIKEN Advanced Science Institute, Wako, Saitama, Japan Address for correspondence: Takashi Angata, Systems Glycobiology Research Group, Chemical Biology Department, RIKEN Advanced Science Institute, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan. angata@riken.jp; Naoyuki Taniguchi, Systems Glycobiology Research Group, Chemical Biology Department, RIKEN Advanced Science Institute, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan. tani52@wd5.so-net.ne.jp Glycobiology has contributed tremendously to the discovery and characterization of cancer-related biomarkers containing glycans (i.e., glyco-biomarkers) and a more detailed understanding of cancer biology. It is now recognized that most chronic diseases involve some elements of chronic inﬂammation; these include cancer, Alzheimer’s disease, and metabolic syndrome (including consequential diabetes mellitus and cardiovascular diseases). By extending the knowledge and experience of the glycobiology community regarding cancer biomarker discovery, we should be able to contribute to the discovery of diagnostic/prognostic glyco-biomarkers of other chronic diseases that involve chronic inﬂammation. Future integration of large-scale “omics”-type data (e.g., genomics, epigenomics, transcriptomics, proteomics, and glycomics) with computational model building, or a systems glycobiology approach, will facilitate such efforts. Keywords: chronic inﬂammation; glyco-biomarker; cancer; Alzheimer’s disease; chronic obstructive pulmonary dis- ease; systems biology Introduction It is now widely recognized that identifying biomarkers reﬂecting disease status is essential not only for reliable diagnosis but also for the develop- ment of effective treatments. 1,2 Although any quan- tiﬁable trait may serve as a biomarker, biomarkers in bodily ﬂuids that require minimally invasive sam- pling are most desirable because repeated sampling is required to monitor disease status and/or treat- ment effectiveness. For this reason, plasma/serum biomarkers are the mainstay for diagnosis and de- cision making in clinical settings. Many potential carbohydrate-related biomarkers (glyco-biomarkers) of various cancers have been discovered and some are used in clinical practice (Table 1). 3,24 Many cancer biomarkers are glyco- proteins. 22 The tumor microenvironment is rich in inﬂammatory cells, such as macrophages, natural killer cells, and cytotoxic T cells, which produce proinﬂammatory stimuli (e.g., proinﬂammatory cy- tokines, lipid metabolites such as prostaglandins, and reactive oxygen species) that likely affect the gly- cosylation patterns of cancer cells and nearby stro- mal cells. Some, if not all, cancer glyco-biomarkers appear to reﬂect this inﬂammatory tumor microenvironment. 25 In this review, we provide a brief overview of glyco-biomarkers related to the inﬂammatory as- pect of cancer as a guiding principle, and discuss possible ways to discover glyco-biomarkers of other inﬂammation-related diseases by integrating vari- ous approaches relevant to glycobiology. Glyco-biomarkers of the inﬂammatory aspect of cancer: a leading paradigm As mentioned earlier, chronic inﬂammation is now considered a major factor contributing to the progression of cancer. 26,27 For example, doi: 10.1111/j.1749-6632.2012.06469.x Ann. N.Y. Acad. Sci. 1253 (2012) 159–169 c  2012 New York Academy of Sciences. 159