MMP expression profiling in recurred stage IB lung cancer

Abstract

We aimed to clarify the prime role of recurrence in stage I lung cancer. To determine the expression profiles, quantitative RT–PCR and real-time PCR were performed subsequently to evaluate the validity of meaningful molecules identified by 0.12 K c-DNA array experiment surveys. In all, 10 lung cancer patients presenting with recurrence of stage IB were selected and compared with 10 stage IB lung cancer patients without recurrence since biopsied 3 years previously. On c-DNA microarray data analysis using pairs of recurred and the corresponding nonrecurred patients, the following genes were found to be upregulated in the recurred cases: matrix metalloproteinase (MMP)-10 in five cases, MMP-12 in two cases, MMP-11, MMP-14, MMP-15, fos, cyclin E2, E2F3, TGF-alpha in each one case. The most frequently upregulated genes in recurred lung cancers were MMP-10 (stromelysin-2) and MMP-12 (macrophage elastase). On transcriptional assay by quantitative RT–PCR and real-time RT–PCR analysis to validate those molecules, both transcripts of MMP-10 and MMP-12 were significantly more upregulated in recurred stage IB lung cancer than in the non-recurred stage IB lung cancer (P=0.004). Transcript levels were identical to c-DNA array data. The protein levels of these entities were also evaluated by immunohistochemistry of archival slides. By immunohistochemistry, MMP-10 monoclonal antibody showed more intense immunoreactivity in the recurred stage IB lung cancer than in the nonrecurred stage IB lung cancer (P=0.0313). Our approach revealed that MMP-10 plays an important role in the recurrence in stage IB lung cancer, irrespective of the histologic type.