Figure 4.

Downregulation of IQGAP1 associates with therapy resistance of PC. (A) IQGAP1 mRNA expression in the Grasso dataset (Oncomine^TM) in androgen sensitive PCs and CRPCs was analyzed. ***: p < 0.001 by 2-tailed Student’s t-test. (B) Prostate specific PTEN^−/− mice at 23 weeks old were either remained as intact status or castrated and maintained for additional 13 weeks. PCs from intact mice (n = 2) and CRPCs from castrated mice (n = 2) were stained for IQGAP1 using IHC. Typical images along with 3-folds enlargement of the indicated regions are included. (C,D) LNCaP xenografts were generated in NOD/SCID mice. Mice were either untreated or castrated when tumors at 100–200 mm³, followed by monitor of PSA increases. Typical images with 3-folds enlargement of the indicated regions (C) and quantifications (D) are shown. Shapiro-Wilk test was used to confirm Gaussian distribution of data. ***: p < 0.001 by 2-tailed Student t-test. IHC images were analyzed using Aperio ImageScope software (Leica Microsystems Inc.); staining intensity was quantified as Histo-scores (HScores). Stromal regions (control) were used as baseline when analyzing final H-score for each sample. (E) IQGAP1 mRNA expression in LNCaP intact vs. CRPC tumors were analyzed using RT-PCR. **: p < 0.01. (F,G) IQGAP1 mRNA expression data, determined by RNA-seq, was retrieved along with the relevant clinical data from the TCGA PanCancer Atlas and MSKCC dataset within cBioPortal. Cutoff points to separate the individual cohort into a high and low recurrence risk group were defined by Maximally Selected Rank Statistics using the R Maxstat package. Kaplan Meier curves and log-rank test were performed using the R Survival package (CRAN - Package survival (r-project.org)). Numbers at risk are indicated.