title: Diagnostic and prognostic impact of desmocollins in human lung cancer.
abstract: OBJECTIVE
  Desmosomes are intercellular junctions that confer strong cell-cell adhesion. Two main members of desmosomal cadherins, desmogleins (DSGs) and desmocollins (DSCs), are involved in carcinogenesis. However, their role in human lung cancer remained elusive. The aims of this study were to analyse the expression of DSCs and to evaluate their clinical application in lung cancer.
  
  
  METHODS
  The expression of DSC1-3 mRNAs was analysed by RT-PCR. The methylation status of DSCs was analysed by demethylation tests and bisulphite sequencing. Protein expression of DSCs in primary lung cancer was evaluated by immunohistochemistry on tissue microarrays.
  
  
  RESULTS
  DSC1-3 mRNAs were downregulated in lung cancer cells, and the expression was restored in four out of seven cell lines, respectively, after 5-aza-2'-deoxycytidine treatment. A heterogeneous methylation pattern was detected by bisulphite sequencing in exon 1 of DSC2 and DSC3. In 199 patients with primary lung cancer, we found that lower protein expression of DSC1 was significantly linked to worse tumour differentiation (p=0.017), DSC3 proteins were more expressed in squamous cell carcinoma (SCC) compared with adenocarcinoma (ADC) (p<0.001), and reduced expression of DSC1 and DSC3 was significantly correlated with poor clinical outcome (p=0.045 and p=0.007, respectively).
  
  
  CONCLUSIONS
  Our data suggest that downregulation of DSC1-3 may be explained by DNA methylation, DSC1 may be a marker for tumour differentiation, DSC3 has a potential diagnostic value in subclassification of non-small cell lung carcinoma into SCC and ADC, and furthermore, DSC1 and DSC3 may be prognostic markers for lung cancer.
authors.affiliation: Institute of Pathology, Jena University Hospital, Jena, Germany.
authors.forename: Tiantian
authors.initials: T
authors.lastname: Cui
authors.forename: Yuan
authors.initials: Y
authors.lastname: Chen
authors.forename: Linlin
authors.initials: L
authors.lastname: Yang
authors.forename: Masoud
authors.initials: M
authors.lastname: Mireskandari
authors.forename: Thomas
authors.initials: T
authors.lastname: Knösel
authors.forename: Qing
authors.initials: Q
authors.lastname: Zhang
authors.forename: Lukas Herbert
authors.initials: LH
authors.lastname: Kohler
authors.forename: Almut
authors.initials: A
authors.lastname: Kunze
authors.forename: Norbert
authors.initials: N
authors.lastname: Presselt
authors.forename: Iver
authors.initials: I
authors.lastname: Petersen
mesh_terms: D000328:Adult; D002277:Carcinoma / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D051187:Desmocollins / Q000378:metabolism*; D015536:Down-Regulation; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology; D009367:Neoplasm Staging; D011379:Prognosis
chemical_list: D051187:Desmocollins