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Copy number alteration of neuropeptides and receptors in multiple cancers.

ABSTRACT: Neuropeptides are peptide hormones used as chemical signals by the neuroendocrine system to communicate between cells. Recently, neuropeptides have been recognized for their ability to act as potent cellular growth factors on many cell types, including cancer cells. However, the molecular mechanism for how this occurs is unknown. To clarify the relationship between neuropeptides and cancer, we manually curated a total of 127 human neuropeptide genes by integrating information from the literature, homologous sequences, and database searches. Using human ligand-receptor interaction data, we first identified an interactome of 226 interaction pairs between 93 neuropeptides and 133 G-protein coupled receptors. We further identified four neuropeptide-receptor functional modules with ten or more genes, all of which were highly mutated in multiple cancers. We have identified a number of neuropeptide signaling systems with both oncogenic and tumour-suppressing roles for cancer progression, such as the insulin-like growth factors. By focusing on the neuroendocrine prostate cancer mutational data, we found prevalent amplification of neuropeptide and receptors in about 72% of samples. In summary, we report the first observation of abundant copy number variations on neuropeptides and receptors, which will be valuable for the design of peptide-based cancer prognosis, diagnosis and treatment.

SUBMITTER: Zhao M

PROVIDER: S-EPMC5496884 | biostudies-other | 2017 Jul

REPOSITORIES: biostudies-other

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Copy number alteration of neuropeptides and receptors in multiple cancers.

Zhao Min M Wang Tianfang T Liu Qi Q Cummins Scott S

Scientific reports 20170704 1

Neuropeptides are peptide hormones used as chemical signals by the neuroendocrine system to communicate between cells. Recently, neuropeptides have been recognized for their ability to act as potent cellular growth factors on many cell types, including cancer cells. However, the molecular mechanism for how this occurs is unknown. To clarify the relationship between neuropeptides and cancer, we manually curated a total of 127 human neuropeptide genes by integrating information from the literature ...[more]

PMID: 28676692

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Project description:PurposeIt has been suggested that dysregulation of transcription factors expression or activity plays significant roles in breast cancer (BC) severity and poor prognosis. Therefore, our study aims to thoroughly evaluate the estrogen-related receptor isoforms (ESRRs) expression and copy number alteration (CNA) status and their association with clinicopathologic characteristics in BC.MethodsA METABRIC dataset consist of 2509 BC patients' samples was obtained from the cBioPortal public domain. The gene expression, putative CNA, and relevant tumor information of ESRRs were retrieved. ESRRs messenger RNA (mRNA) expression in BC cell lines was obtained from the Cancer Cell Line Encyclopedia (CCLE). Association and correlation analysis of ESRRs expression with BC clinicopathologic characteristics and molecular subtype were performed. Kaplan-Meier survival analysis was conducted to evaluate the prognostic value of ESRRs expression on patient survival.ResultsESRRα expression correlated negatively with patients' age and overall survival, whereas positively correlated with tumor size, the number of positive lymph nodes, and Nottingham prognostic index (NPI). Conversely, ESRRγ expression was positively correlated with patients' age and negatively correlated with NPI. ESRRα and ESRRγ expression were significantly associated with tumor grade, expression of hormone receptors, human epidermal growth factor receptor 2 (HER2), and molecular subtype, whereas ESRRβ was only associated with tumor stage. A significant and distinct association of each of ESRRs CNA with various clinicopathologic and prognostic factors was also observed. Kaplan-Meier survival analysis demonstrated no significant difference for survival curves among BC patients with high or low expression of ESRRα, β, or γ. On stratification, high ESRRα expression significantly reduced survival among premenopausal patients, patients with grade I/II, and early-stage disease. In BC cell lines, only ESRRα expression was significantly higher in HER2-positive cells. No significant association was observed between ESRRβ expression and any of the clinicopathologic characteristics examined.ConclusionsIn this clinical dataset, ESRRα and ESRRγ mRNA expression and CNA show a significant correlation and association with distinct clinicopathologic and prognostic parameters known to influence treatment outcomes; however, ESRRβ failed to show a robust role in BC pathogenesis. ESRRα and ESRRγ can be employed as therapeutic targets in BC-targeted therapy. However, the role of ESRRβ in BC pathogenesis remains unclear.

Dataset Information

Copy number alteration of neuropeptides and receptors in multiple cancers.

Publications

Copy number alteration of neuropeptides and receptors in multiple cancers.

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