Effective Prediction of Prostate Cancer Recurrence through the IQGAP1 Network.
Cancers (Basel)
; 13(3)2021 Jan 23.
Article
em En
| MEDLINE
| ID: mdl-33498739
ABSTRACT
IQGAP1 expression was analyzed in (1) primary prostate cancer, (2) xenografts produced from LNCaP, DU145, and PC3 cells, 3) tumor of PTEN-/- and TRAMP mice, and (3) castration resistant PC (CRPC) produced by LNCaP xenografts and PTEN-/- mice. IQGAP1 downregulations occurred in CRPC and advanced PCs. The downregulations were associated with rapid PC recurrence in the TCGA PanCancer (n = 492, p = 0.01) and MSKCC (n = 140, p = 4 × 10-6) cohorts. Differentially expressed genes (n = 598) relative to IQGAP1 downregulation were identified with enrichment in chemotaxis, cytokine signaling, and others along with reductions in immune responses. A novel 27-gene signature (Sig27gene) was constructed from these DEGs through random division of the TCGA cohort into a Training and Testing population. The panel was validated using an independent MSKCC cohort. Sig27gene robustly predicts PC recurrence at (hazard ratio) HR 2.72 and p < 2 × 10-16 in two independent PC cohorts. The prediction remains significant after adjusting for multiple clinical features. The novel and robust nature of Sig27gene underlie its great translational potential as a prognostic biomarker to predict PC relapse risk in patients with primary PC.
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MEDLINE
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Ano de publicação:
2021
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Article