title: An integrative multi-platform analysis for discovering biomarkers of osteosarcoma.
abstract: BACKGROUND
  SELDI-TOF-MS (Surface Enhanced Laser Desorption/Ionization-Time of Flight-Mass Spectrometry) has become an attractive approach for cancer biomarker discovery due to its ability to resolve low mass proteins and high-throughput capability. However, the analytes from mass spectrometry are described only by their mass-to-charge ratio (m/z) values without further identification and annotation. To discover potential biomarkers for early diagnosis of osteosarcoma, we designed an integrative workflow combining data sets from both SELDI-TOF-MS and gene microarray analysis.
  
  
  METHODS
  After extracting the information for potential biomarkers from SELDI data and microarray analysis, their associations were further inferred by link-test to identify biomarkers that could likely be used for diagnosis. Immuno-blot analysis was then performed to examine whether the expression of the putative biomarkers were indeed altered in serum from patients with osteosarcoma.
  
  
  RESULTS
  Six differentially expressed protein peaks with strong statistical significances were detected by SELDI-TOF-MS. Four of the proteins were up-regulated and two of them were down-regulated. Microarray analysis showed that, compared with an osteoblastic cell line, the expression of 653 genes was changed more than 2 folds in three osteosarcoma cell lines. While expression of 310 genes was increased, expression of the other 343 genes was decreased. The two sets of biomarkers candidates were combined by the link-test statistics, indicating that 13 genes were potential biomarkers for early diagnosis of osteosarcoma. Among these genes, cytochrome c1 (CYC-1) was selected for further experimental validation.
  
  
  CONCLUSIONS
  Link-test on datasets from both SELDI-TOF-MS and microarray high-throughput analysis can accelerate the identification of tumor biomarkers. The result confirmed that CYC-1 may be a promising biomarker for early diagnosis of osteosarcoma.
authors.affiliation: Department of Orthopaedics, Tenth People's Hospital, Tongji University, Shanghai, PR China. litrue2004@yahoo.com.cn
authors.forename: Guodong
authors.initials: G
authors.lastname: Li
authors.forename: Wenjuan
authors.initials: W
authors.lastname: Zhang
authors.forename: Huazong
authors.initials: H
authors.lastname: Zeng
authors.forename: Lei
authors.initials: L
authors.lastname: Chen
authors.forename: Wenjing
authors.initials: W
authors.lastname: Wang
authors.forename: Jilong
authors.initials: J
authors.lastname: Liu
authors.forename: Zhiyu
authors.initials: Z
authors.lastname: Zhang
authors.forename: Zhengdong
authors.initials: Z
authors.lastname: Cai
mesh_terms: D000293:Adolescent; D000328:Adult; D014408:Biomarkers, Tumor / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D001798:Blood Proteins / Q000737:chemistry; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D002648:Child; D003575:Cytochromes c1 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D012516:Osteosarcoma / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D001798:Blood Proteins; D003575:Cytochromes c1