title: Clinical validation of colorectal cancer biomarkers identified from bioinformatics analysis of public expression data.
abstract: OBJECTIVE
  Identification of novel biomarkers of cancer is important for improved diagnosis, prognosis, and therapeutic intervention. This study aimed to identify marker genes of colorectal cancer (CRC) by combining bioinformatics analysis of gene expression data and validation experiments using patient samples and to examine the potential connection between validated markers and the established oncogenes such as c-Myc and K-ras.
  
  
  METHODS
  Publicly available data from GenBank and Oncomine were meta-analyzed leading to 34 candidate marker genes of CRC. Multiple case-matched normal and tumor tissues were examined by RT-PCR for differential expression, and 9 genes were validated as CRC biomarkers. Statistical analyses for correlation with major clinical parameters were carried out, and RNA interference was used to examine connection with major oncogenes.
  
  
  RESULTS
  We show with high confidence that 9 (ECT2, ETV4, DDX21, RAN, S100A11, RPS4X, HSPD1, CKS2, and C9orf140) of the 34 candidate genes are expressed at significantly elevated levels in CRC tissues compared to normal tissues. Furthermore, high-level expression of RPS4X was associated with nonmucinous cancer cell type and that of ECT2 with lack of lymphatic invasion while upregulation of CKS2 was correlated with early tumor stage and lack of family history of CRC. We also demonstrate that RPS4X and DDX21 are regulatory targets of c-Myc and ETV4 is downstream to K-ras signaling.
  
  
  CONCLUSIONS
  We have identified multiple novel biomarkers of CRC. Further analyses of their function and connection to signaling pathways may reveal potential value of these biomarkers in diagnosis, prognosis, and treatment of CRC.
authors.affiliation: Ewha Research Center for Systems Biology, Seoul, Korea.
authors.forename: Yeonjoo
authors.initials: Y
authors.lastname: Jung
authors.forename: Sanghyuk
authors.initials: S
authors.lastname: Lee
authors.forename: Hyung-Seok
authors.initials: HS
authors.lastname: Choi
authors.forename: Soon-Nam
authors.initials: SN
authors.lastname: Kim
authors.forename: Eunyoung
authors.initials: E
authors.lastname: Lee
authors.forename: Youngah
authors.initials: Y
authors.lastname: Shin
authors.forename: Jihae
authors.initials: J
authors.lastname: Seo
authors.forename: Bumjin
authors.initials: B
authors.lastname: Kim
authors.forename: Yeonhwa
authors.initials: Y
authors.lastname: Jung
authors.forename: Wan Kyu
authors.initials: WK
authors.lastname: Kim
authors.forename: Ho-Kyung
authors.initials: HK
authors.lastname: Chun
authors.forename: Woo Yong
authors.initials: WY
authors.lastname: Lee
authors.forename: Jaesang
authors.initials: J
authors.lastname: Kim
mesh_terms: D017500:Adenovirus E1A Proteins / Q000235:genetics; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism; D019295:Computational Biology; D053487:DEAD-box RNA Helicases / Q000235:genetics; D030541:Databases, Genetic; D005260:Female; D020869:Gene Expression Profiling / Q000706:statistics & numerical data; D015972:Gene Expression Regulation, Neoplastic; D056726:Genetic Association Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D011518:Proto-Oncogene Proteins / Q000235:genetics; D050783:Proto-Oncogene Proteins c-ets; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D016283:Proto-Oncogene Proteins p21(ras) / Q000378:metabolism; D012269:Ribosomal Proteins / Q000235:genetics
chemical_list: D017500:Adenovirus E1A Proteins; D014408:Biomarkers, Tumor; C079853:ETV4 protein, human; C489427:MYC protein, human; D011518:Proto-Oncogene Proteins; D050783:Proto-Oncogene Proteins c-ets; D016271:Proto-Oncogene Proteins c-myc; D012269:Ribosomal Proteins; C031798:ribosomal protein S4; C501726:DDX21 protein, human; D053487:DEAD-box RNA Helicases; D016283:Proto-Oncogene Proteins p21(ras)