title: Low-molecular-mass secretome profiling identifies HMGA2 and MIF as prognostic biomarkers for oral cavity squamous cell carcinoma.
abstract: The profiling of cancer cell secretomes is considered to be a good strategy for identifying cancer-related biomarkers, but few studies have focused on identifying low-molecular-mass (LMr) proteins (<15 kDa) in cancer cell secretomes. Here, we used tricine-SDS-gel-assisted fractionation and LC-MS/MS to systemically identify LMr proteins in the secretomes of five oral cavity squamous cell carcinoma (OSCC) cell lines. Cross-matching of these results with nine OSCC tissue transcriptome datasets allowed us to identify 33 LMr genes/proteins that were highly upregulated in OSCC tissues and secreted/released from OSCC cells. Immunohistochemistry and quantitative real-time PCR were used to verify the overexpression of two candidates, HMGA2 and MIF, in OSCC tissues. The overexpressions of both proteins were associated with cervical metastasis, perineural invasion, deeper tumor invasion, higher overall stage, and a poorer prognosis for post-treatment survival. Functional assays further revealed that both proteins promoted the migration and invasion of OSCC cell lines in vitro. Collectively, our data indicate that the tricine-SDS-gel/LC-MS/MS approach can be used to efficiently identify LMr proteins from OSCC cell secretomes, and suggest that HMGA2 and MIF could be potential tissue biomarkers for OSCC.
authors.affiliation: 1] Departments of Otolaryngology-Head &Neck Surgery, Chang Gung Memorial Hospital, Tao-Yuan, Taiwan [2] Molecular Medicine Research Center, Chang Gung University, Tao-Yuan, Taiwan.
authors.forename: Kai-Ping
authors.initials: KP
authors.lastname: Chang
authors.affiliation: Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Tao-Yuan, Taiwan.
authors.forename: Shih-Jie
authors.initials: SJ
authors.lastname: Lin
authors.affiliation: Departments of Otolaryngology-Head &Neck Surgery, Chang Gung Memorial Hospital, Tao-Yuan, Taiwan.
authors.forename: Shiau-Chin
authors.initials: SC
authors.lastname: Liu
authors.affiliation: 1] Departments of Otolaryngology-Head &Neck Surgery, Chang Gung Memorial Hospital, Tao-Yuan, Taiwan [2] Molecular Medicine Research Center, Chang Gung University, Tao-Yuan, Taiwan.
authors.forename: Jui-Shan
authors.initials: JS
authors.lastname: Yi
authors.affiliation: 1] Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Tao-Yuan, Taiwan [2] Molecular Medicine Research Center, Chang Gung University, Tao-Yuan, Taiwan.
authors.forename: Kun-Yi
authors.initials: KY
authors.lastname: Chien
authors.affiliation: 1] Molecular Medicine Research Center, Chang Gung University, Tao-Yuan, Taiwan [2] Department of Medical Research, Chang Gung Memorial Hospital, Tao-Yuan, Taiwan.
authors.forename: Lang-Ming
authors.initials: LM
authors.lastname: Chi
authors.affiliation: Department of Plastic &Reconstructive Surgery, Chang Gung Memorial Hospital, Tao-Yuan, Taiwan.
authors.forename: Huang-Kai
authors.initials: HK
authors.lastname: Kao
authors.affiliation: Molecular Medicine Research Center, Chang Gung University, Tao-Yuan, Taiwan.
authors.forename: Ying
authors.initials: Y
authors.lastname: Liang
authors.affiliation: Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Tao-Yuan, Taiwan.
authors.forename: Yu-Tsun
authors.initials: YT
authors.lastname: Lin
authors.affiliation: 1] Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Tao-Yuan, Taiwan [2] Molecular Medicine Research Center, Chang Gung University, Tao-Yuan, Taiwan.
authors.forename: Yu-Sun
authors.initials: YS
authors.lastname: Chang
authors.affiliation: 1] Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Tao-Yuan, Taiwan [2] Molecular Medicine Research Center, Chang Gung University, Tao-Yuan, Taiwan [3] Department of Cell and Molecular Biology, College of Medicine, Chang Gung University, Tao-Yuan, Taiwan.
authors.forename: Jau-Song
authors.initials: JS
authors.lastname: Yu
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement; D005260:Female; D025743:HMGA2 Protein / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D019746:Intramolecular Oxidoreductases / Q000737:chemistry / Q000378:metabolism*; D008263:Macrophage Migration-Inhibitory Factors / Q000737:chemistry / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D008970:Molecular Weight; D009062:Mouth Neoplasms / Q000175:diagnosis / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D011379:Prognosis; D020543:Proteome / Q000378:metabolism*; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D025743:HMGA2 Protein; D008263:Macrophage Migration-Inhibitory Factors; D020543:Proteome; D019746:Intramolecular Oxidoreductases; C515598:MIF protein, human