Dataset Information

Comparison of metastatic castration-resistant prostate cancer in bone with other sites: clinical characteristics, molecular features and immune status.

ABSTRACT: Metastatic castration-resistant prostate cancer (mCRPC) is the lethal stage and the leading cause of death in prostate cancer patients, among which bone metastasis is the most common site. Here in this article, we downloaded the gene expression data and clinical information from online dataset. We found that prostate cancer metastasis in bone is prone to have higher prostate-specific antigen (PSA) and longer time on first-line androgen receptor signaling inhibitors (ARSI). A total of 1,263 differentially expressed genes (DEGs) were identified and results of functional enrichment analysis indicated the enrichment in categories related to cell migration, cancer related pathways and metabolism. We identified the top 20 hub genes from the PPI network and analyzed the clinical characteristics correlated with these hub genes. Finally, we analyzed the immune cell abundance ratio of each sample in different groups. Our results reveal the different clinical characteristics, the immune cell infiltration pattern in different sites of mCRPC, and identify multiple critical related genes and pathways, which provides basis for individualized treatment.

SUBMITTER: Xu Z

PROVIDER: S-EPMC8023235 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Comparison of metastatic castration-resistant prostate cancer in bone with other sites: clinical characteristics, molecular features and immune status.

Xu Zhengquan Z Ding Yanhong Y Lu Wei W Zhang Ke K Wang Fei F Ding Guanxiong G Wang Jianqing J

PeerJ 20210331

Metastatic castration-resistant prostate cancer (mCRPC) is the lethal stage and the leading cause of death in prostate cancer patients, among which bone metastasis is the most common site. Here in this article, we downloaded the gene expression data and clinical information from online dataset. We found that prostate cancer metastasis in bone is prone to have higher prostate-specific antigen (PSA) and longer time on first-line androgen receptor signaling inhibitors (ARSI). A total of 1,263 diffe ...[more]

PMID: 33859877

Similar Datasets

Project description:BackgroundEnzalutamide is a novel antiandrogen with proven efficacy in metastatic castration-resistant prostate cancer (mCRPC).ObjectiveTo evaluate enzalutamide's effects on cancer and on androgens in blood and bone marrow, and associate these with clinical observations.Design, setting, and participantsIn this prospective phase 2 study, 60 patients with bone mCRPC received enzalutamide 160mg orally daily and had transilial bone marrow biopsies before treatment and at 8 wk of treatment.Outcome measurements and statistical analysisAndrogen signaling components (androgen receptor [AR], AR splice variant 7 (ARV7), v-ets avian erythroblastosis virus E26 oncogene homolog [ERG], cytochrome P450, family 17, subfamily A, polypeptide 1 [CYP17]) and molecules implicated in mCRPC progression (phospho-Met, phospho-Src, glucocorticoid receptor, Ki67) were assessed by immunohistochemistry; testosterone, cortisol, and androstenedione concentrations were assessed by liquid chromatography-tandem mass spectrometry; AR copy number was assessed by real-time polymerase chain reaction. Descriptive statistics were applied.Results and limitationsMedian time to treatment discontinuation was 22 wk (95% confidence interval, 19.9-29.6). Twenty-two (37%) patients exhibited primary resistance to enzalutamide, discontinuing treatment within 4 mo. Maximal prostate-specific antigen (PSA) decline ≥ 50% and ≥ 90% occurred in 27 (45%) and 13 (22%) patients, respectively. Following 8 wk of treatment, bone marrow and circulating testosterone levels increased. Pretreatment tumor nuclear AR overexpression (> 75%) and CYP17 (> 10%) expression were associated with benefit (p = 0.018). AR subcellular localization shift from the nucleus was confirmed in eight paired samples (with PSA decline) of 23 evaluable paired samples. Presence of an ARV7 variant was associated with primary resistance to enzalutamide (p = 0.018). Limited patient numbers warrant further validation.ConclusionsThe observed subcellular shift of AR from the nucleus and increased testosterone concentration provide the first evidence in humans that enzalutamide suppresses AR signaling while inducing an adaptive feedback. Persistent androgen signaling in mCRPC was predictive of benefit and ARV7 was associated with primary resistance.Patient summaryWe report a first bone biopsy study in metastatic prostate cancer in humans that searched for predictors of outcome of enzalutamide therapy. Benefit is linked to a pretreatment androgen-signaling signature.Trial registrationClinicalTrials.gov identifier NCT01091103.

Project description:BackgroundRadium-223 is a targeted alpha-particle therapy that improves survival in men with metastatic castration resistant prostate cancer (mCRPC), particularly in men with elevated serum levels of bone alkaline phosphatase (B-ALP). We hypothesized that osteomimicry, a form of epithelial plasticity leading to an osteoblastic phenotype, may contribute to intralesional deposition of radium-223 and subsequent irradiation of the tumor microenvironment.MethodsWe conducted a pharmacodynamic study (NCT02204943) of radium-223 in men with bone mCRPC. Prior to and three and six months after radium-223 treatment initiation, we collected CTCs and metastatic biopsies for phenotypic characterization and CTC genomic analysis. The primary objective was to describe the impact of radium-223 on the prevalence of CTC B-ALP over time. We measured radium-223 decay products in tumor and surrounding normal bone during treatment. We validated genomic findings in a separate independent study of men with bone metastatic mCRPC (n = 45) and publicly accessible data of metastatic CRPC tissues.ResultsWe enrolled 20 men with symptomatic bone predominant mCRPC and treated with radium-223. We observed greater radium-223 radioactivity levels in metastatic bone tumor containing biopsies compared with adjacent normal bone. We found evidence of persistent Cellsearch CTCs and B-ALP (+) CTCs in the majority of men over time during radium-223 therapy despite serum B-ALP normalization. We identified genomic gains in osteoblast mimicry genes including gains of ALPL, osteopontin, SPARC, OB-cadherin and loss of RUNX2, and validated genomic alterations or increased expression at the DNA and RNA level in an independent cohort of 45 men with bone-metastatic CRPC and in 150 metastatic biopsies from men with mCRPC.ConclusionsOsteomimicry may contribute in part to the uptake of radium-223 within bone metastases and may thereby enhance the therapeutic benefit of this bone targeting radiotherapy.

Dataset Information

Comparison of metastatic castration-resistant prostate cancer in bone with other sites: clinical characteristics, molecular features and immune status.

Publications

Comparison of metastatic castration-resistant prostate cancer in bone with other sites: clinical characteristics, molecular features and immune status.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets