PPM1D as a novel biomarker for prostate cancer after radical prostatectomy

Abstract

Protein phosphatase magnesium-dependent 1 delta (PPM1D) is involved in several types of cancer. The current study examined the role of PPM1D expression in prostate cancer (PCa) tissues and in PCa cell lines. Expression of PPM1D was evaluated using immunohistochemistry in 234 PCa tissues after radical prostatectomy and 80 benign prostatic hyperplasia (BPH) tissues. The associations of PPM1D expression with clinicopathological parameters and survival were analyzed. In vitro, tumor cells were transfected with small interfering RNA targeting PPM1D (siPPM1D) or si-Scramble, and the cell proliferation, migration and invasion were determined. We found that PPM1D expression was significantly higher in PCa tissues than that in BPH tissues. PPM1D expression was positively correlated with Gleason score (p=0.022), T stage (p=0.015) and lymph node status (p=0.016). Kaplan-Meier curve analysis showed that patients with positive PPM1D expression had shorter biochemical recurrence-free survival and overall survival. Furthermore, multivariate analyses showed that PPM1D expression was an independent predictor of both biochemical recurrence-free (hazard ratio=3.437, 95% confidence interval=1.154-6.209, p=0.016) and overall survival (hazard ratio=5.026, 95% confidence interval=2.545-8.109, p=0.007). Knockdown of PPM1D inhibited the proliferation, migration and invasion capabilities of PC-3 and LNCaP cells. PPM1D expression may predict for both overall and biochemical recurrence-free survival in patients after radical prostatectomy for PCa. Elevated PPM1D expression plays a key role in progression of PCa.

Keywords: PPM1D; biomarker; prognosis; prostate cancer.