Polo-like kinase-1 as a potential prognostic marker of prostate cancer utilizing ORIEN data.

Abstract

384 Background: Polo-Like Kinase-1(PLK1) is one of the key regulators in G2/M cell cycle. Preclinical studies have shown that PLK1 might be involved in treatment resistance in prostate cancer (PCa). PLK1 overexpression by immunohistochemistry is associated with higher Gleason grade and thus PLK1 could play a role in PCa tumorigenesis. In this study, we utilized a different methodology by using RNA-seq PLK1 expression and correlated with clinical outcomes. Methods: Patients with all stages of prostate adenocarcinoma diagnosed between 2014 and 2020 from nine participating members of the Oncology Research Information Exchange Network (ORIEN) were included in the study. Tumor RNA-seq was analyzed for PLK1 expression and associated with clinical data obtained from ORIEN AVATAR. PLK1 expression was stratified into high expression (defined as ≥75th percentile of PLK1 mRNA expression) vs. low expression (≤75th percentile). Univariate and multivariate Cox proportional hazard model were used to compare overall survival between patients with low vs high PLK1 expression adjusting for age, race, PSA and stage. Results: A total of 452 tumors were evaluated for PLK1 expression. Of those, 241 (53.3%) had high PLK1 and 211 (46.7%) had low PLK1 expression. Median age at diagnosis for high and low PLK1 expression was 64.5 and 63.2 years respectively. The majority of patients were Caucasian in both groups. In high PLK1 group, 93 (65%) had localized high risk/very high risk disease, 27 (19%) had localized intermediate risk, 20 (14%) had metastatic vs. 97 (63%), 38 (25%) and 18(12%) respectively in low PLK1 group. Gleason ≥ 8 and PSA <20 were seen slightly more in high PLK1 compared to low PLK1; 40% vs 33% and 96% vs.94% respectively. The median follow-up time was 2.74 years in low PLK1 group and 2.71 years in high PLK1 group. There was no difference between PLK1 low vs. high expression for age, race, stage, PSA and Gleason grade. There was no difference in overall survival between low PLK1 and high PLK1 expression by univariate analysis (p=0.86; HR 1.09) or after adjusting for multivariate analysis (p=0.85; HR 1.12). Conclusions: In our study, we did not find RNA-seq PLK1 expression as a potential prognostic marker for prostate cancer. There was no survival difference between low PLK1 vs. high PLK1 expression.