Figure 4
Figure 4. Aurora-A and -B are overexpressed in patients with high CI and are suitable therapeutic targets for these high-risk patients. (A) Among the differentially expressed genes are some candidate genes previously implicated in mediating centrosome amplification. Of these, the expression of both STK6 and AURKB, which code for aurora-A and aurora-B, respectively, was significantly higher in patients with high CI (3.46 ± 2.49 vs 1.07 ± 1.05, t test P < .0001, and 2.60 ± 2.43 vs 0.9 ± 0.85, t test P < .001, respectively) and may represent potentially novel therapeutic targets in these poor-prognosis patients. (B) The expression of aurora-A and -B was significantly higher in HMCLs, and a significant number of tumors (MGUS, SMM, and MM) have expression above normal plasma cells (normalized gene expression greater than 1). (C) Expression of aurora-A and -B was detected by IHC. Staining for aurora-A and -B is cytoplasmic and nuclear, respectively. The staining is generally stronger for aurora-B than -A. For aurora-B staining in the left panel, the positive cells are indicated by close arrows. For both aurora-A and -B staining in the left and right panels, image inserts show area of staining at higher magnification. Images are at 10 × magnification except for image inserts that are at 40×. The images are captured on the Olympus BX51 microscope using the Olympus DP71 CCD camera and MicroSuite 5 software (Olympus Imaging America). Adobe Photoshop CS version 8 is then used to resize the images. (D) Protein expression of aurora-A and -B correlated with gene expression. When the cases with different percentage of positive-staining cells are grouped together, there is a corresponding increase in gene expression in the patients with higher percentage of positive cells (P = .006 for aurora-A and P = .002 for aurora-B), suggesting correlation between gene and protein expression. (E) Survival of patients with high CI (regardless of STK6 or AURB expression, although 80% of patients with high CI have high STK6 and/or AURKB expression) and those overexpressing both STK6 and AURKB is significantly shorter (n = 49 and n = 14, median OS, 42.7 and 39.8 months, respectively, log-rank P = .0005) than patients overexpressing just one of these genes (n = 33, median OS not reached) or those not overexpressing either gene (n = 255, median OS not reached).

Aurora-A and -B are overexpressed in patients with high CI and are suitable therapeutic targets for these high-risk patients. (A) Among the differentially expressed genes are some candidate genes previously implicated in mediating centrosome amplification. Of these, the expression of both STK6 and AURKB, which code for aurora-A and aurora-B, respectively, was significantly higher in patients with high CI (3.46 ± 2.49 vs 1.07 ± 1.05, t test P < .0001, and 2.60 ± 2.43 vs 0.9 ± 0.85, t test P < .001, respectively) and may represent potentially novel therapeutic targets in these poor-prognosis patients. (B) The expression of aurora-A and -B was significantly higher in HMCLs, and a significant number of tumors (MGUS, SMM, and MM) have expression above normal plasma cells (normalized gene expression greater than 1). (C) Expression of aurora-A and -B was detected by IHC. Staining for aurora-A and -B is cytoplasmic and nuclear, respectively. The staining is generally stronger for aurora-B than -A. For aurora-B staining in the left panel, the positive cells are indicated by close arrows. For both aurora-A and -B staining in the left and right panels, image inserts show area of staining at higher magnification. Images are at 10 × magnification except for image inserts that are at 40×. The images are captured on the Olympus BX51 microscope using the Olympus DP71 CCD camera and MicroSuite 5 software (Olympus Imaging America). Adobe Photoshop CS version 8 is then used to resize the images. (D) Protein expression of aurora-A and -B correlated with gene expression. When the cases with different percentage of positive-staining cells are grouped together, there is a corresponding increase in gene expression in the patients with higher percentage of positive cells (P = .006 for aurora-A and P = .002 for aurora-B), suggesting correlation between gene and protein expression. (E) Survival of patients with high CI (regardless of STK6 or AURB expression, although 80% of patients with high CI have high STK6 and/or AURKB expression) and those overexpressing both STK6 and AURKB is significantly shorter (n = 49 and n = 14, median OS, 42.7 and 39.8 months, respectively, log-rank P = .0005) than patients overexpressing just one of these genes (n = 33, median OS not reached) or those not overexpressing either gene (n = 255, median OS not reached).

Close Modal
This Feature Is Available To Subscribers Only

or Create an Account

Close Modal
Close Modal