Microarray analysis of gene-expression profiles in diffuse large B-cell lymphoma: identification of genes related to disease progression.

To identify genes that are associated with progression of malignant lymphoma, the expression profiles of 18,432 genes were analyzed in diffuse large B-cell lymphomas at early (stages I and II, 6 cases) and advanced stages (stages III and IV, 9 cases) by means of cDNA microarrays. By comparing expression profiles between localized and advanced lymphomas, a number of genes that were differentially expressed were identified: 48 genes with increased expression and 30 genes with reduced expression in advanced-stage diffuse large B-cell lymphomas. Increased expression of MPHOSPH1, RUVBL1, CHN2, PSA and CDC10 genes, and reduced expression of COL1A2, COL4A1, FBLN5, CLECSF6, MIC2, CAV1 and S100A10 genes in the advanced lymphoma group were confirmed by semi-quantitative reverse transcription-PCR. RUVBL1 and PSA expression was further confirmed by real-time quantitative PCR, whose results paralleled the microarray data. The highly expressed genes encode proteins that promote cell proliferation and the genes with reduced expression encode adhesion proteins and target protein for cytotoxic T-lymphocytes. These findings suggested that analysis with cDNA microarrays is a useful approach for identifying genes related to tumor progression and their products could be potential tumor markers or disease-specific targets for anti-tumor therapy.