کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8456870 | 1548782 | 2017 | 11 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Overexpression of MUC1 and Genomic Alterations in Its Network Associate with Prostate Cancer Progression
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
تحقیقات سرطان
پیش نمایش صفحه اول مقاله

چکیده انگلیسی
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 PTENâ/â mice and LNCaP xenografts. Elevations in MUC1 expression occur in CRPC. Among nine patients with hormone-naïve 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/β-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 β-catenin mutants are identified in PCs leading to a rapid onset of death and recurrence. Genomic alterations in APC and CTNNB1/β-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.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neoplasia - Volume 19, Issue 11, November 2017, Pages 857-867
Journal: Neoplasia - Volume 19, Issue 11, November 2017, Pages 857-867
نویسندگان
Xiaozeng Lin, Yan Gu, Anil Kapoor, Fengxiang Wei, Tariq Aziz, Diane Ojo, Yanzhi Jiang, Michael Bonert, Bobby Shayegan, Huixiang Yang, Khalid Al-Nedawi, Pierre Major, Damu Tang,