title: Genome-wide gene expression profile analyses identify CTTN as a potential prognostic marker in esophageal cancer.
abstract: OBJECTIVE
  Esophageal squamous cell carcinoma (ESCC) is one of the most common fatal malignances of the digestive tract. Its prognosis is poor mainly due to the lack of reliable markers for early detection and prognostic prediction. Here we aim to identify the molecules involved in ESCC carcinogenesis and those as potential markers for prognosis and as new molecular therapeutic targets.
  
  
  METHODS
  We performed genome-wide gene expression profile analyses of 10 primary ESCCs and their adjacent normal tissues by cDNA microarrays representing 47,000 transcripts and variants. Candidate genes were then validated by semi quantitative reverse transcription-PCR (RT-PCR), tissue microarrays (TMAs) and immunohistochemistry (IHC) staining.
  
  
  RESULTS
  Using an arbitrary cutoff line of signal log ratio of ≥1.5 or ≤-1.5, we observed 549 up-regulated genes and 766 down-regulated genes in ESCCs compared with normal esophageal tissues. The functions of 302 differentially expressed genes were associated with cell metabolism, cell adhesion and immune response. Several candidate deregulated genes including four overexpressed (CTTN, DMRT2, MCM10 and SCYA26) and two underexpressed (HMGCS2 and SORBS2) were subsequently verified, which can be served as biomarkers for ESCC. Moreover, overexpression of cortactin (CTTN) was observed in 126/198 (63.6%) of ESCC cases and was significantly associated with lymph node metastasis (P = 0.000), pathologic stage (P = 0.000) and poor survival (P<0.001) of ESCC patients. Furthermore, a significant correlation between CTTN overexpression and shorter disease-specific survival rate was found in different subgroups of ESCC patient stratified by the pathologic stage (P<0.05).
  
  
  CONCLUSIONS
  Our data provide valuable information for establishing molecules as candidates for prognostic and/or as therapeutic targets.
authors.affiliation: Department of Clinical Oncology, the First Affiliated Hospital, Zhengzhou University, Zhengzhou, China.
authors.forename: Pei
authors.initials: P
authors.lastname: Lu
authors.affiliation: Department of Clinical Oncology, the First Affiliated Hospital, Zhengzhou University, Zhengzhou, China.
authors.forename: Junjing
authors.initials: J
authors.lastname: Qiao
authors.affiliation: Department of Clinical Oncology, the First Affiliated Hospital, Zhengzhou University, Zhengzhou, China.
authors.forename: Wei
authors.initials: W
authors.lastname: He
authors.affiliation: Department of Clinical Oncology, the First Affiliated Hospital, Zhengzhou University, Zhengzhou, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Clinical Oncology, the First Affiliated Hospital, Zhengzhou University, Zhengzhou, China.
authors.forename: Yongxu
authors.initials: Y
authors.lastname: Jia
authors.affiliation: Department of Clinical Oncology, the First Affiliated Hospital, Zhengzhou University, Zhengzhou, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Medicine and Therapeutics, the Chinese University of Hong Kong, Hong Kong, China.
authors.forename: Senwei
authors.initials: S
authors.lastname: Tang
authors.affiliation: Department of Medicine and Therapeutics, the Chinese University of Hong Kong, Hong Kong, China.
authors.forename: Li
authors.initials: L
authors.lastname: Fu
authors.affiliation: Department of Clinical Oncology, the First Affiliated Hospital, Zhengzhou University, Zhengzhou, China.
authors.forename: Yanru
authors.initials: Y
authors.lastname: Qin
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D045744:Cell Line, Tumor; D051356:Cortactin / Q000235:genetics* / Q000378:metabolism; D004848:Epithelium / Q000378:metabolism / Q000473:pathology; D004938:Esophageal Neoplasms / Q000235:genetics*; D000077277:Esophageal Squamous Cell Carcinoma; D004947:Esophagus / Q000378:metabolism / Q000473:pathology; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D015894:Genome, Human / Q000235:genetics*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016016:Proportional Hazards Models; D012044:Regression Analysis; D015203:Reproducibility of Results; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D014408:Biomarkers, Tumor; C495868:CTTN protein, human; D051356:Cortactin