Bronchial epithelial cells as a new source for differential transcriptome analysis after lung transplantation.
OBJECTIVE
The early diagnosis of chronic organ rejection after lung transplantation (LTx) is currently hampered by the lack of reliable diagnostic markers. The present study aims to establish the procedure of gene expression profiling in bronchial epithelial cells for the identification of candidate genes that might prove useful in the early diagnosis.


METHODS
Twenty-three patients who underwent lung transplantations were investigated at a time point when no clinical signs of bronchiolitis obliterans syndrome (BOS) were apparent. Bronchial epithelial cells were obtained by bronchial brushing. Gene expression profiles were determined using a human whole-genome cDNA microarray (Stanford Faculty, Stanford, CA, USA).


RESULTS
Unsupervised hierarchical cluster analysis revealed that the samples from LTx patients can be clearly distinguished from the comparison group. We also found that the samples from LTx patients with the same underlying disease do not form major clusters of gene expression pattern. Using biostatistical analysis, 'haemoglobin beta', expressed by alveolar type II and Clara cells, and CD99, involved in inflammatory processes, were identified comparing lung transplantation and comparison group.


CONCLUSIONS
Thus, global expression analyses of bronchial epithelial cells might be a new approach to identify diagnostic markers, especially if patients with LTx are monitored sequentially and if patients with and without BOS are compared.
Skawran
Britta
B
Institute of Cell and Molecular Pathology, Hannover Medical School, 30625 Hannover, Germany.
Dierich
Martin
M
Steinemann
Doris
D
Hohlfeld
Jens
J
Haverich
Axel
A
Schlegelberger
Brigitte
B
Welte
Tobias
T
von Neuhoff
Nils
N
D000071443:12E7 Antigen; D015703:Antigens, CD / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D001980:Bronchi / Q000378:metabolism* / Q000473:pathology; D001989:Bronchiolitis Obliterans / Q000175:diagnosis* / Q000209:etiology; D015815:Cell Adhesion Molecules / Q000378:metabolism; D042241:Early Diagnosis; D004847:Epithelial Cells / Q000378:metabolism; D020869:Gene Expression Profiling / Q000379:methods; D006801:Humans; D016040:Lung Transplantation / Q000009:adverse effects*; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D010865:Pilot Projects; D020545:Respiratory Mucosa / Q000378:metabolism* / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D015854:Up-Regulation; D055544:beta-Globins / Q000378:metabolism
D000071443:12E7 Antigen; D015703:Antigens, CD; D015415:Biomarkers; C061828:CD99 protein, human; D015815:Cell Adhesion Molecules; D055544:beta-Globins