title: Decoding the s-nitrosoproteomic atlas in individualized human colorectal cancer tissues using a label-free quantitation strategy.
abstract: The abnormal S-nitrosylation induced by the overexpression and activation of inducible nitric oxide synthase (iNOS) modulates many human diseases, such as inflammation and cancer. To delineate the pathophysiological S-nitrosoproteome in cancer patients, we report an individualized S-nitrosoproteomic strategy with a label-free method for the site-specific quantification of S-nitrosylation in paired tumor and adjacent normal tissues from 11 patients with colorectal cancer (CRC). This study provides not only the first endogenous human S-nitrosoproteomic atlas but also the first individualized human tissue analysis, identifying 174 S-nitrosylation sites in 94 proteins. Fourteen novel S-nitrosylation sites with a high frequency of elevated levels in 11 individual patients were identified. An individualized S-nitrosylation quantitation analysis revealed that the detected changes in S-nitrosylation were regulated by both the expression level and the more dramatic post-translational S-nitrosylation of the targeted proteins, such as thioredoxin, annexin A4, and peroxiredoxin-4. These endogenous S-nitrosylated proteins illustrate the network of inflammation/cancer-related and redox reactions mediated by various S-nitrosylation sources, including iNOS, transnitrosylase, or iron-sulfur centers. Given the demonstrated sensitivity of individualized tissue analysis, this label-free approach may facilitate the study of the vastly under-represented S-nitrosoproteome and enable a better understanding of the effect of endogenous S-nitrosylation in cancer.
authors.affiliation: Institute of Chemistry, Academia Sinica , Taipei, Taiwan.
authors.forename: Yi-Ju
authors.initials: YJ
authors.lastname: Chen
authors.forename: Wei-Chieh
authors.initials: WC
authors.lastname: Ching
authors.forename: Jinn-Shiun
authors.initials: JS
authors.lastname: Chen
authors.forename: Tzong-Yi
authors.initials: TY
authors.lastname: Lee
authors.forename: Cheng-Tsung
authors.initials: CT
authors.lastname: Lu
authors.forename: Hsiao-Chiao
authors.initials: HC
authors.lastname: Chou
authors.forename: Pei-Yi
authors.initials: PY
authors.lastname: Lin
authors.forename: Kay-Hooi
authors.initials: KH
authors.lastname: Khoo
authors.forename: Jenn-Han
authors.initials: JH
authors.lastname: Chen
authors.forename: Yu-Ju
authors.initials: YJ
authors.lastname: Chen
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D015153:Blotting, Western; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000601:surgery; D003545:Cysteine / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D057285:Precision Medicine; D011506:Proteins / Q000032:analysis* / Q000737:chemistry / Q000378:metabolism*; D040901:Proteomics / Q000379:methods*; D012016:Reference Values; D015203:Reproducibility of Results; D012710:Serum Albumin, Bovine / Q000032:analysis; D053719:Tandem Mass Spectrometry / Q000379:methods; D013879:Thioredoxins / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D011506:Proteins; C491203:TXN protein, human; D012710:Serum Albumin, Bovine; D013879:Thioredoxins; C496319:NOS2 protein, human; D052247:Nitric Oxide Synthase Type II; D003545:Cysteine
keywords: S-nitrosylation; biotin switch; colorectal cancer; label-free quantitation