title: Gene expression profile of peripheral blood in colorectal cancer.
abstract: OBJECTIVE
  Optimal molecular markers for detecting colorectal cancer (CRC) in a blood-based assay were evaluated.
  
  
  METHODS
  A matched (by variables of age and sex) case-control design (111 CRC and 227 non-cancer samples) was applied. Total RNAs isolated from the 338 blood samples were reverse-transcribed, and the relative transcript levels of candidate genes were analyzed. The training set was made of 162 random samples of the total 338 samples. A logistic regression analysis was performed, and odds ratios for each gene were determined between CRC and non-cancer. The samples (n = 176) in the testing set were used to validate the logistic model, and an inferred performance (generality) was verified. By pooling 12 public microarray datasets(GSE 4107, 4183, 8671, 9348, 10961, 13067, 13294, 13471, 14333, 15960, 17538, and 18105), which included 519 cases of adenocarcinoma and 88 controls of normal mucosa, we were able to verify the selected genes from logistic models and estimate their external generality.
  
  
  RESULTS
  The logistic regression analysis resulted in the selection of five significant genes (P < 0.05; MDM2, DUSP6, CPEB4, MMD, and EIF2S3), with odds ratios of 2.978, 6.029, 3.776, 0.538 and 0.138, respectively. The five-gene model performed stably for the discrimination of CRC cases from controls in the training set, with accuracies ranging from 73.9% to 87.0%, a sensitivity of 95% and a specificity of 95%. In addition, a good performance in the test set was obtained using the discrimination model, providing 83.5% accuracy, 66.0% sensitivity, 92.0% specificity, a positive predictive value of 89.2% and a negative predictive value of 73.0%. Multivariate logistic regressions analyzed 12 pooled public microarray data sets as an external validation. Models that provided similar expected and observed event rates in subgroups were termed well calibrated. A model in which MDM2, DUSP6, CPEB4, MMD, and EIF2S3 were selected showed the result in logistic regression analysis (H-L P = 0.460, R2= 0.853, AUC = 0.978, accuracy = 0.949, specificity = 0.818 and sensitivity = 0.971).
  
  
  CONCLUSIONS
  A novel gene expression profile was associated with CRC and can potentially be applied to blood-based detection assays.
authors.affiliation: Yu-Tien Chang, Yun-Wen Shih, Chen-En Jian, Chiao-Huang Lin, Chien-Ting Chen, Yi-Syuan Wu, Ke-Shin Lin, Chi-Ming Chu, Division of Biomedical Statistics and Informatics, School of Public Health, National Defense Medical Center, Taipei 114, Taiwan.
authors.forename: Yu-Tien
authors.initials: YT
authors.lastname: Chang
authors.affiliation: Yu-Tien Chang, Yun-Wen Shih, Chen-En Jian, Chiao-Huang Lin, Chien-Ting Chen, Yi-Syuan Wu, Ke-Shin Lin, Chi-Ming Chu, Division of Biomedical Statistics and Informatics, School of Public Health, National Defense Medical Center, Taipei 114, Taiwan.
authors.forename: Chi-Shuan
authors.initials: CS
authors.lastname: Huang
authors.affiliation: Yu-Tien Chang, Yun-Wen Shih, Chen-En Jian, Chiao-Huang Lin, Chien-Ting Chen, Yi-Syuan Wu, Ke-Shin Lin, Chi-Ming Chu, Division of Biomedical Statistics and Informatics, School of Public Health, National Defense Medical Center, Taipei 114, Taiwan.
authors.forename: Chung-Tay
authors.initials: CT
authors.lastname: Yao
authors.affiliation: Yu-Tien Chang, Yun-Wen Shih, Chen-En Jian, Chiao-Huang Lin, Chien-Ting Chen, Yi-Syuan Wu, Ke-Shin Lin, Chi-Ming Chu, Division of Biomedical Statistics and Informatics, School of Public Health, National Defense Medical Center, Taipei 114, Taiwan.
authors.forename: Sui-Lung
authors.initials: SL
authors.lastname: Su
authors.affiliation: Yu-Tien Chang, Yun-Wen Shih, Chen-En Jian, Chiao-Huang Lin, Chien-Ting Chen, Yi-Syuan Wu, Ke-Shin Lin, Chi-Ming Chu, Division of Biomedical Statistics and Informatics, School of Public Health, National Defense Medical Center, Taipei 114, Taiwan.
authors.forename: Harn-Jing
authors.initials: HJ
authors.lastname: Terng
authors.affiliation: Yu-Tien Chang, Yun-Wen Shih, Chen-En Jian, Chiao-Huang Lin, Chien-Ting Chen, Yi-Syuan Wu, Ke-Shin Lin, Chi-Ming Chu, Division of Biomedical Statistics and Informatics, School of Public Health, National Defense Medical Center, Taipei 114, Taiwan.
authors.forename: Hsiu-Ling
authors.initials: HL
authors.lastname: Chou
authors.affiliation: Yu-Tien Chang, Yun-Wen Shih, Chen-En Jian, Chiao-Huang Lin, Chien-Ting Chen, Yi-Syuan Wu, Ke-Shin Lin, Chi-Ming Chu, Division of Biomedical Statistics and Informatics, School of Public Health, National Defense Medical Center, Taipei 114, Taiwan.
authors.forename: Yu-Ching
authors.initials: YC
authors.lastname: Chou
authors.affiliation: Yu-Tien Chang, Yun-Wen Shih, Chen-En Jian, Chiao-Huang Lin, Chien-Ting Chen, Yi-Syuan Wu, Ke-Shin Lin, Chi-Ming Chu, Division of Biomedical Statistics and Informatics, School of Public Health, National Defense Medical Center, Taipei 114, Taiwan.
authors.forename: Kang-Hua
authors.initials: KH
authors.lastname: Chen
authors.affiliation: Yu-Tien Chang, Yun-Wen Shih, Chen-En Jian, Chiao-Huang Lin, Chien-Ting Chen, Yi-Syuan Wu, Ke-Shin Lin, Chi-Ming Chu, Division of Biomedical Statistics and Informatics, School of Public Health, National Defense Medical Center, Taipei 114, Taiwan.
authors.forename: Yun-Wen
authors.initials: YW
authors.lastname: Shih
authors.affiliation: Yu-Tien Chang, Yun-Wen Shih, Chen-En Jian, Chiao-Huang Lin, Chien-Ting Chen, Yi-Syuan Wu, Ke-Shin Lin, Chi-Ming Chu, Division of Biomedical Statistics and Informatics, School of Public Health, National Defense Medical Center, Taipei 114, Taiwan.
authors.forename: Chian-Yu
authors.initials: CY
authors.lastname: Lu
authors.affiliation: Yu-Tien Chang, Yun-Wen Shih, Chen-En Jian, Chiao-Huang Lin, Chien-Ting Chen, Yi-Syuan Wu, Ke-Shin Lin, Chi-Ming Chu, Division of Biomedical Statistics and Informatics, School of Public Health, National Defense Medical Center, Taipei 114, Taiwan.
authors.forename: Ching-Huang
authors.initials: CH
authors.lastname: Lai
authors.affiliation: Yu-Tien Chang, Yun-Wen Shih, Chen-En Jian, Chiao-Huang Lin, Chien-Ting Chen, Yi-Syuan Wu, Ke-Shin Lin, Chi-Ming Chu, Division of Biomedical Statistics and Informatics, School of Public Health, National Defense Medical Center, Taipei 114, Taiwan.
authors.forename: Chen-En
authors.initials: CE
authors.lastname: Jian
authors.affiliation: Yu-Tien Chang, Yun-Wen Shih, Chen-En Jian, Chiao-Huang Lin, Chien-Ting Chen, Yi-Syuan Wu, Ke-Shin Lin, Chi-Ming Chu, Division of Biomedical Statistics and Informatics, School of Public Health, National Defense Medical Center, Taipei 114, Taiwan.
authors.forename: Chiao-Huang
authors.initials: CH
authors.lastname: Lin
authors.affiliation: Yu-Tien Chang, Yun-Wen Shih, Chen-En Jian, Chiao-Huang Lin, Chien-Ting Chen, Yi-Syuan Wu, Ke-Shin Lin, Chi-Ming Chu, Division of Biomedical Statistics and Informatics, School of Public Health, National Defense Medical Center, Taipei 114, Taiwan.
authors.forename: Chien-Ting
authors.initials: CT
authors.lastname: Chen
authors.affiliation: Yu-Tien Chang, Yun-Wen Shih, Chen-En Jian, Chiao-Huang Lin, Chien-Ting Chen, Yi-Syuan Wu, Ke-Shin Lin, Chi-Ming Chu, Division of Biomedical Statistics and Informatics, School of Public Health, National Defense Medical Center, Taipei 114, Taiwan.
authors.forename: Yi-Syuan
authors.initials: YS
authors.lastname: Wu
authors.affiliation: Yu-Tien Chang, Yun-Wen Shih, Chen-En Jian, Chiao-Huang Lin, Chien-Ting Chen, Yi-Syuan Wu, Ke-Shin Lin, Chi-Ming Chu, Division of Biomedical Statistics and Informatics, School of Public Health, National Defense Medical Center, Taipei 114, Taiwan.
authors.forename: Ke-Shin
authors.initials: KS
authors.lastname: Lin
authors.affiliation: Yu-Tien Chang, Yun-Wen Shih, Chen-En Jian, Chiao-Huang Lin, Chien-Ting Chen, Yi-Syuan Wu, Ke-Shin Lin, Chi-Ming Chu, Division of Biomedical Statistics and Informatics, School of Public Health, National Defense Medical Center, Taipei 114, Taiwan.
authors.forename: Thomas
authors.initials: T
authors.lastname: Wetter
authors.affiliation: Yu-Tien Chang, Yun-Wen Shih, Chen-En Jian, Chiao-Huang Lin, Chien-Ting Chen, Yi-Syuan Wu, Ke-Shin Lin, Chi-Ming Chu, Division of Biomedical Statistics and Informatics, School of Public Health, National Defense Medical Center, Taipei 114, Taiwan.
authors.forename: Chi-Wen
authors.initials: CW
authors.lastname: Chang
authors.affiliation: Yu-Tien Chang, Yun-Wen Shih, Chen-En Jian, Chiao-Huang Lin, Chien-Ting Chen, Yi-Syuan Wu, Ke-Shin Lin, Chi-Ming Chu, Division of Biomedical Statistics and Informatics, School of Public Health, National Defense Medical Center, Taipei 114, Taiwan.
authors.forename: Chi-Ming
authors.initials: CM
authors.lastname: Chu
mesh_terms: D000230:Adenocarcinoma / Q000097:blood / Q000235:genetics* / Q000473:pathology; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood / Q000235:genetics*; D016009:Chi-Square Distribution; D015179:Colorectal Neoplasms / Q000097:blood / Q000235:genetics* / Q000473:pathology; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D020022:Genetic Predisposition to Disease; D006801:Humans; D016015:Logistic Models; D008297:Male; D015999:Multivariate Analysis; D016017:Odds Ratio; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D011237:Predictive Value of Tests; D015203:Reproducibility of Results; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D014408:Biomarkers, Tumor
keywords: Colorectal cancer; Gene expression; Internet; Microarray