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Diagnostic and prognostic impact of desmocollins in human lung cancer
  1. Tiantian Cui1,
  2. Yuan Chen1,
  3. Linlin Yang1,
  4. Masoud Mireskandari1,
  5. Thomas Knösel2,
  6. Qing Zhang1,
  7. Lukas Herbert Kohler1,
  8. Almut Kunze3,
  9. Norbert Presselt4,
  10. Iver Petersen1
  1. 1Institute of Pathology, Jena University Hospital, Jena, Germany
  2. 2Institute of Pathology, Ludwig-Maximilians-University Munich, Munich, Germany
  3. 3Pathology Institute at the Central Clinic Bad Berka, Bad Berka, Germany
  4. 4Thoracic and Vascular Surgery, Central Clinic Bad Berka GmbH, Bad Berka, Germany
  1. Correspondence to Dr Iver Petersen, Institute of Pathology, Jena University Hospital, Friedrich-Schiller-University Jena, Ziegelmühlenweg 1, 07743 Jena, Germany; iver.petersen{at}med.uni-jena.de

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.

  • Lung Cancer
  • Diagnosis
  • Molecular Oncology

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