Expression profile of early lung adenocarcinoma: identification of MRP3 as a molecular marker for early progression

Early lung adenocarcinoma is well-recognized as a small-sized non-invasive adenocarcinoma or localized non-mucinous bronchioloalveolar carcinoma (LNMBAC); however, the molecular events associated with these early lesions are not clear. To determine the genes involved in tumorigenesis at the early stage of lung adenocarcinoma, we compared the mRNA expression profiles of LNMBAC and normal lungs with an oligonucleotide array. Immunohistochemical analyses were performed to confirm the expression of detected genes. We identified 183 differentially expressed genes, of which 15 were up-regulated and 168 down-regulated. Among them, most up-regulated genes, such as AQP3 and Claudin-4, were expressed in both adenocarcinoma cells and type II alveolar pneumocytes, corresponding to the histological similarity between these cell types. However, multidrug resistant protein 3 (MRP3) was only expressed on tumour cell membranes and not in type II alveolar pneumocytes, as confirmed by immunohistochemistry. Moreover, the number of MRP3-positive cells significantly increased from AAH (the precursor lesion of lung adenocarcinoma) to LNMBAC. We conclude that MRP3 could be a novel molecular marker for LNMBAC, whose expression increases during the early progression of tumourigenesis.