title: TMPRSS4 Expression as a Marker of Recurrence in Patients with Lung Cancer.
abstract: BACKGROUND
  Postoperative recurrence is a significant problem associated with a poor prognosis. However, there is currently no consensus regarding biomarkers of recurrence.
  
  
  METHODS
  We performed a microarray expression analysis using a combination of tumor tissues (n=2) and cell lines. We prioritized and validated candidate protein expression levels in the primary tumors.
  
  
  RESULTS
  We prioritized 18 genes found to be up-regulated by more than four-fold in both A925LPE3 cell lines compared to the A925L cell line (lung adenocarcinoma) and in the cases of recurrence versus no recurrence, in order to find genes highly causative of metastasis. Among them, we selected transmembrane protease, serine 4 (TMPRSS4) and identified positive expression of TMPRSS4 in 93 (57.8%) patients. A significant negative association was observed only between the TMPRSS4 expression level and the N status. The univariate logistic regression models indicated that TMPRSS4 expression was an independent predictor of recurrence, as was the T and N status.
  
  
  CONCLUSIONS
  TMPRSS4 expression is associated with postoperative recurrence. In addition, the current survival curves demonstrated that TMPRSS4 expression is associated with statistically significant differences in survival among patients with lung adenocarcinoma. TMPRSS4 staining can be used to predict the prognosis of such patients after surgery.
authors.affiliation: Second Department of Surgery, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Chikaishi
authors.affiliation: Second Department of Surgery, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan hidetaka@med.uoeh-u.ac.jp.
authors.forename: Hidetaka
authors.initials: H
authors.lastname: Uramoto
authors.affiliation: Second Department of Surgery, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Koyanagi
authors.affiliation: Departments of Pathology and Cell Biology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.
authors.forename: Sohsuke
authors.initials: S
authors.lastname: Yamada
authors.affiliation: Division of Medical Oncology, Cancer Research Institute, Kanazawa University, Ishikawa, Japan.
authors.forename: Seiji
authors.initials: S
authors.lastname: Yano
authors.affiliation: Second Department of Surgery, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.
authors.forename: Fumihiro
authors.initials: F
authors.lastname: Tanaka
mesh_terms: D000230:Adenocarcinoma / Q000201:enzymology* / Q000235:genetics / Q000401:mortality / Q000473:pathology / Q000601:surgery; D000077192:Adenocarcinoma of Lung; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D016009:Chi-Square Distribution; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D016015:Logistic Models; D008175:Lung Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000401:mortality / Q000473:pathology / Q000601:surgery; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D020411:Oligonucleotide Array Sequence Analysis; D011237:Predictive Value of Tests; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D008565:Membrane Proteins; D012697:Serine Endopeptidases; C528837:TMPRSS4 protein, human
keywords: Lung cancer; TMPRSS4; prognosis; recurrence; surgery