%0 Journal Article
%T Overexpression of MUC1 and Genomic Alterations in Its Network Associate with Prostate Cancer Progression
%A Anil Kapoor
%A Bobby Shayegan
%A Damu Tang
%A Diane Ojo
%A Fengxiang Wei
%A Huixiang Yang
%A Khalid Al-Nedawi
%A Michael Bonert
%A Pierre Major
%A Tariq Aziz
%A Xiaozeng Lin
%A Yan Gu
%A Yanzhi Jiang
%J Archive of "Neoplasia (New York, N.Y.)".
%D 2017
%R 10.1016/j.neo.2017.06.006
%X We investigate the association of MUC1 with castration-resistant prostate cancer (CRPC), bone metastasis, and PC recurrence. MUC1 expression was studied in patient-derived bone metastasis and CRPCs produced by prostate-specific PTEN£¿/£¿ mice and LNCaP xenografts. Elevations in MUC1 expression occur in CRPC. Among nine patients with hormone-na£¿ve bone metastasis, eight express MUC1 in 61% to 100% of PC cells. Utilizing cBioPortal PC genomic data, we organized a training (n = 300), testing (n = 185), and validation (n = 194) cohort. Using the Cox model, a nine-gene signature was derived, including eight genes from a MUC1-related network (APC, CTNNB1/¦Â-catenin, GALNT10, GRB2, LYN, SIGLEC1, SOS1, and ZAP70) and FAM84B. Genomic alterations in these genes reduce disease-free survival (DFS) in the training (P = .00161), testing (P = .00699), entire (training + testing, P = 5.557e-5), and a validation cohort (P = 3.326e-5). The signature independently predicts PC recurrence [hazard ratio (HR) = 1.731; 95% confidence interval (CI): 1.104-2.712; P = .0167] after adjusting for known clinical factors and stratifies patients with high risk of PC recurrence using the median (HR 2.072; 95% CI: 1.245-3.450, P = .0051) and quartile 3 (HR 3.707, 95% CI: 1.949-7.052, P = 6.51e-5) scores. Several novel ¦Â-catenin mutants are identified in PCs leading to a rapid onset of death and recurrence. Genomic alterations in APC and CTNNB1/¦Â-catenin reduce DFS in two independent PC cohorts (n = 485, P = .0369; n = 84, P = .0437). The nine-gene signature also associates with reductions in overall survival (P = .0458) and DFS (P = .0163) in melanoma patients (n = 367). MUC1 upregulation is associated with CRPC and bone metastasis. A nine-gene signature derived from a MUC1 network predicts PC recurrence
%K ADT
%K androgen deprivation therapy
%K BR
%K biochemical recurrence
%K RP
%K radical prostatectomy
%K WHO
%K the World Health Organization
%U https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5605493/