Clinical Significance of Polo-Like Kinase 4 as a Marker for Advanced Tumor Stage and Dismal Prognosis in Patients With Surgical Gastric Cancer

Abstract

Objective: This study aimed to investigate the correlation of polo-like kinase 4 with clinicopathological features and survival profiles in patients with gastric cancer.

Methods: This retrospective study was conducted based on the clinical data from 289 eligible patients with gastric cancer who received resection. Polo-like kinase 4 expression in adjacent tissue and tumor tissue was determined by immunohistochemical assay and semiquantified scoring method using immunohistochemical score by staining intensity score multiplying staining density score. Based on the total immunohistochemical score (ranged from 0 to 12), the polo-like kinase 4 expression was classified as low expression (immunohistochemical: 0-3) and high expression (immunohistochemical: 4-12); furthermore, high expression was divided into high+ expression (immunohistochemical: 4-6), high++ expression (immunohistochemical: 7-9), and high+++ expression (immunohistochemical: 10-12).

Results: Polo-like kinase 4 expression was elevated in tumor tissue compared with adjacent tissue. Tumor polo-like kinase 4 high expression correlated with increased T stage and Tumor, Node, Metastasis (TNM) stage, while, it did not correlate with age, gender, current smoke, current drink, chronic complications, Helicobacter pylori infection, tumor location, pathological grade, or N stage. Besides, higher tumor polo-like kinase 4 expression correlated with shorter disease-free survival and overall survival. Subsequently, multivariate Cox proportional hazards regression analysis showed that higher tumor polo-like kinase 4 expression was an independent predictive factor for worse disease-free survival but not for overall survival.

Conclusion: Polo-like kinase 4 possesses the clinical significance as a biomarker for aiding prognostication and facilitating postoperative tumor management in patients with gastric cancer.

Keywords: T stage; TNM stage; gastric cancer; polo-like kinase 4; prognosis.

Figure 1.

PLK4 expression in tumor tissue and adjacent tissue. Representative IHC staining images of tumor tissue with PLK4 low expression, PLK4 high+ expression, PLK4 high++ expression, and PLK4 high+++ expression (A), and adjacent tissue with PLK4 low expression, PLK4 high+ expression, PLK4 high++ expression, and PLK4 high+++ expression (B). Comparison of the percentage of PLK4 low expression and the percentage of PLK4 high expression between tumor tissue and adjacent tissue (C). Comparison of the percentage of PLK4 low expression, the percentage of PLK4 high+ expression, the percentage of PLK4 high++ expression, and the percentage of PLK4 high+++ expression between tumor tissue and adjacent tissue (D). Comparisons were assessed by McNemar test. P < .05 was considered significant. IHC indicates immunohistochemical; PLK4, polo-like kinase 4.

Figure 2.

Correlation of PLK4 expression with tumor features. Comparisons of tumor location (A), pathological grade (B), T stage (C), N stage (D), and TNM stage (E) between patients with tumor PLK4 high expression and patients with tumor PLK4 low expression. Comparisons between patients with tumor PLK4 high expression and patients with tumor PLK4 low expression were assessed by χ² test or Wilcoxon rank sum test. P < .05 was considered significant. PLK4 indicates polo-like kinase 4.

Figure 3.

Negative correlation of PLK4 expression with DFS. Comparison of DFS between patients with tumor PLK4 high expression and patients with tumor PLK4 low expression (A). Comparison of DFS among patients with tumor PLK4 high+++ expression, patients with tumor PLK4 high++ expression, patients with tumor PLK4 high+ expression, and patients with tumor PLK4 low expression (B). Kaplan-Meier curve and log-rank test were used to compare DFS between patients with tumor PLK4 high expression and patients with tumor PLK4 low expression. P < .05 was considered significant. DFS indicates disease-free survival; PLK4, polo-like kinase 4.

Figure 4.

Negative correlation of PLK4 expression with OS. Comparison of OS between patients with tumor PLK4 high expression and patients with tumor PLK4 low expression (A). Comparison of OS among patients with tumor PLK4 high+++ expression, patients with tumor PLK4 high++ expression, patients with tumor PLK4 high+ expression, and patients with tumor PLK4 low expression (B). Kaplan-Meier curve and log-rank test were used to compare OS between patients with tumor PLK4 high expression and patients with tumor PLK4 low expression. P < .05 was considered significant. OS indicates overall survival; PLK4, polo-like kinase 4.