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. 2022 Mar 10:12:840950.
doi: 10.3389/fonc.2022.840950. eCollection 2022.

CRMP4 CpG Hypermethylation Predicts Upgrading to Gleason Score ≥ 8 in Prostate Cancer

Xiao-Ping Qin  1 , Qi-Ji Lu  2 , Cheng-Huizi Yang  3 , Jue Wang  4 , Jian-Fan Chen  1 , Kan Liu  5 , Xin Chen  6 , Jing Zhou  7 , Yu-Hang Pan  7 , Yong-Hong Li  8 , Shan-Cheng Ren  9 , Jiu-Min Liu  10 , Wei-Peng Liu  11 , Hui-Jun Qian  12 , Xian-Lin Yi  13 , Cai-Yong Lai  1 , Li-Jun Qu  1 , Xin Gao  14 , Yu-Sheng Xu  15 , Zheng Chen  1 , Yu-Min Zhuo  1
Affiliations

CRMP4 CpG Hypermethylation Predicts Upgrading to Gleason Score ≥ 8 in Prostate Cancer

Xiao-Ping Qin et al. Front Oncol. .

Abstract

Background: This study determined the predictive value of CRMP4 promoter methylation in prostate tissues collected by core needle biopsies for a postoperative upgrade of Gleason Score (GS) to ≥8 in patients with low-risk PCa.

Method: A retrospective analysis of the clinical data was conducted from 631 patients diagnosed with low-risk PCa by core needle biopsy at multiple centers and then underwent Radical Prostatectomy (RP) from 2014-2019. Specimens were collected by core needle biopsy to detect CRMP4 promoter methylation. The pathologic factors correlated with the postoperative GS upgrade to ≥8 were analyzed by logistic regression. The cut-off value for CRMP4 promoter methylation in the prostate tissues collected by core needle biopsy was estimated from the ROC curve in patients with a postoperative GS upgrade to ≥8.

Result: Multivariate logistic regression showed that prostate volume, number of positive cores, and CRMP4 promoter methylation were predictive factors for a GS upgrade to ≥8 (OR: 0.94, 95% CI: 0.91-0.98, P=0.003; OR: 3.16, 95% CI: 1.81-5.53, P<0.001; and OR: 1.43, 95% CI: 1.32-1.55, P<0.001, respectively). The positive predictive rate was 85.2%, the negative predictive rate was 99.3%, and the overall predictive rate was 97.9%. When the CRMP4 promoter methylation rate was >18.00%, the low-risk PCa patients were more likely to escalate to high-risk patients. The predictive sensitivity and specificity were 86.9% and 98.8%, respectively. The area under the ROC curve (AUC) was 0.929 (95% CI: 0.883-0.976; P<0.001). The biochemical recurrence (BCR)-free survival, progression-free survival (PFS), and cancer-specific survival (CSS) were worse in patients with CRMP4 methylation >18.0% and postoperative GS upgrade to ≥8 than in patients without an upgrade (P ≤ 0.002).

Conclusion: A CRMP4 promoter methylation rate >18.00% in prostate cancer tissues indicated that patients were more likely to escalate from low-to-high risk after undergoing an RP. We recommend determining CRMP4 promoter methylation before RP for low-risk PCa patients.

Keywords: CRMP4 promoter methylation; biochemical recurrence; gleason score upgrade; pelvic lymph node dissection; prostate cancer.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
ROC curves for predicting a postoperative upgrade in GS to ≥8. V, prostate volume; PC, Positive cores; C4, collapsin response mediator protein 4.
Figure 2
Figure 2
Comparison of pathological features between patients with a postoperative upgrade in GS to ≥8 and those without such an upgrade. GS, gleason score; SVI, seminal vesicle invasion; SM, surgical margin; LNI, lymph node invasion.
Figure 3
Figure 3
BCR-free survival in patients with biopsy C4 ≤ 18.0% and biopsy C4>18.0% (A). Clinically progression-free survival in patients with biopsy C4 ≤ 18.0% and biopsy C4>18.0% (B).Cancer specific survival in patients with biopsy C4 ≤ 18.0% and biopsy C4>18.0% (C). C4, collapsin response mediator protein 4 methylation.
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