Frontiers in Oncology (Aug 2022)

Evaluation and multi-institutional validation of a novel urine biomarker lncRNA546 to improve the diagnostic specificity of prostate cancer in PSA gray-zone

  • Fei Liu,
  • Xiaolei Shi,
  • Fangming Wang,
  • Sujun Han,
  • Dong Chen,
  • Xu Gao,
  • Linhui Wang,
  • Qiang Wei,
  • Nianzeng Xing,
  • Shancheng Ren

DOI
https://doi.org/10.3389/fonc.2022.946060
Journal volume & issue
Vol. 12

Abstract

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Background and objectivesProstate specific antigen (PSA) is currently the most commonly used biomarker for prostate cancer diagnosis. However, when PSA is in the gray area of 4-10 ng/ml, the diagnostic specificity of prostate cancer is extremely low, leading to overdiagnosis in many clinically false-positive patients. This study was trying to discover and evaluate a novel urine biomarker long non-coding RNA (lncRNA546) to improve the diagnostic accuracy of prostate cancer in PSA gray-zone.MethodsA cohort study including consecutive 440 participants with suspected prostate cancer was retrospectively conducted in multi-urology centers. LncRNA546 scores were calculated with quantitative real-time polymerase chain reaction. The area under the receiver operating characteristic curve (AUROC), decision curve analysis (DCA) and a biopsy-specific nomogram were utilized to evaluate the potential for clinical application. Logistic regression model was constructed to confirm the predictive power of lncRNA546.ResultsLncRNA546 scores were sufficient to discriminate positive and negative biopsies. ROC analysis showed a higher AUC for lncRNA546 scores than prostate cancer antigen 3 (PCA3) scores (0.78 vs. 0.66, p<0.01) in the overall cohort. More importantly, the AUC of lncRNA546 (0.80) was significantly higher than the AUCs of total PSA (0.57, p=0.02), percentage of free PSA (%fPSA) (0.64, p=0.04) and PCA3 (0.63, p<0.01) in the PSA 4-10 ng/ml cohort. A base model constructed by multiple logistic regression analysis plus lncRNA546 scores improved the predictive accuracy (PA) from 79.8% to 86.3% and improved AUC results from 0.862 to 0.915. DCA showed that the base model plus lncRNA546 displayed greater net benefit at threshold probabilities beyond 15% in the PSA 4-10 ng/ml cohort.ConclusionLncRNA546 is a promising novel biomarker for the early detection of prostate cancer, especially in the PSA 4-10 ng/ml cohort.

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