Unknown

Dataset Information

0

Overexpression of MUC1 and Genomic Alterations in Its Network Associate with Prostate Cancer Progression.


ABSTRACT: 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-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/?-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 ?-catenin mutants are identified in PCs leading to a rapid onset of death and recurrence. Genomic alterations in APC and CTNNB1/?-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.

SUBMITTER: Lin X 

PROVIDER: S-EPMC5605493 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

altmetric image

Publications

Overexpression of MUC1 and Genomic Alterations in Its Network Associate with Prostate Cancer Progression.

Lin Xiaozeng X   Gu Yan Y   Kapoor Anil A   Wei Fengxiang F   Aziz Tariq T   Ojo Diane D   Jiang Yanzhi Y   Bonert Michael M   Shayegan Bobby B   Yang Huixiang H   Al-Nedawi Khalid K   Major Pierre P   Tang Damu D  

Neoplasia (New York, N.Y.) 20170918 11


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<sup>-/-</sup> 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  ...[more]

Similar Datasets

| S-EPMC6969104 | biostudies-literature
| S-EPMC2768451 | biostudies-literature
| S-EPMC3490108 | biostudies-literature
| S-EPMC6159966 | biostudies-literature
| S-EPMC2676873 | biostudies-literature
| S-EPMC5751811 | biostudies-other
2019-12-02 | GSE139335 | GEO
| S-EPMC8669499 | biostudies-literature
| S-EPMC2441856 | biostudies-literature
| S-EPMC7190998 | biostudies-literature