scholarly journals Multi-Omics Analyses Detail Metabolic Reprogramming in Lipids, Carnitines, and Use of Glycolytic Intermediates between Prostate Small Cell Neuroendocrine Carcinoma and Prostate Adenocarcinoma

Metabolites ◽  
2019 ◽  
Vol 9 (5) ◽  
pp. 82 ◽  
Author(s):  
Bei Gao ◽  
Hui-Wen Lue ◽  
Jennifer Podolak ◽  
Sili Fan ◽  
Ying Zhang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Lines ◽  
Neuroendocrine Carcinoma ◽  
Prostate Adenocarcinoma ◽  
Small Cell ◽  
Gene Set Enrichment Analysis ◽  
Metabolic Reprogramming ◽  
Small Cell Neuroendocrine Carcinoma ◽  
Gene Sets ◽  
Glycolytic Intermediates

As the most common cancer in men, prostate cancer is molecularly heterogeneous. Contributing to this heterogeneity are the poorly understood metabolic adaptations of the two main types of prostate cancer, i.e., adenocarcinoma and small cell neuroendocrine carcinoma (SCNC), the latter being more aggressive and lethal. Using transcriptomics, untargeted metabolomics and lipidomics profiling on LASCPC-01 (prostate SCNC) and LNCAP (prostate adenocarcinoma) cell lines, we found significant differences in the cellular phenotypes of the two cell lines. Gene set enrichment analysis on the transcriptomics data showed 62 gene sets were upregulated in LASCPC-01, while 112 gene sets were upregulated in LNCAP. ChemRICH analysis on metabolomics and lipidomics data revealed a total of 25 metabolite clusters were significantly different. LASCPC-01 exhibited a higher glycolytic activity and lower levels of triglycerides, while the LNCAP cell line showed increases in one-carbon metabolism as an exit route of glycolytic intermediates and a decrease in carnitine, a mitochondrial lipid transporter. Our findings pinpoint differences in prostate neuroendocrine carcinoma versus prostate adenocarcinoma that could lead to new therapeutic targets in each type.

scholarly journals A basal stem cell signature identifies aggressive prostate cancer phenotypes

2015 ◽  
Vol 112 (47) ◽  
pp. E6544-E6552 ◽  
Author(s):  
Bryan A. Smith ◽  
Artem Sokolov ◽  
Vladislav Uzunangelov ◽  
Robert Baertsch ◽  
Yulia Newton ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Stem Cells ◽  
Stem Cell ◽  
Neuroendocrine Carcinoma ◽  
Late Stage ◽  
Metastatic Prostate Cancer ◽  
Small Cell ◽  
Basal Cells ◽  
Small Cell Neuroendocrine Carcinoma ◽  
Aggressive Prostate Cancer

Evidence from numerous cancers suggests that increased aggressiveness is accompanied by up-regulation of signaling pathways and acquisition of properties common to stem cells. It is unclear if different subtypes of late-stage cancer vary in stemness properties and whether or not these subtypes are transcriptionally similar to normal tissue stem cells. We report a gene signature specific for human prostate basal cells that is differentially enriched in various phenotypes of late-stage metastatic prostate cancer. We FACS-purified and transcriptionally profiled basal and luminal epithelial populations from the benign and cancerous regions of primary human prostates. High-throughput RNA sequencing showed the basal population to be defined by genes associated with stem cell signaling programs and invasiveness. Application of a 91-gene basal signature to gene expression datasets from patients with organ-confined or hormone-refractory metastatic prostate cancer revealed that metastatic small cell neuroendocrine carcinoma was molecularly more stem-like than either metastatic adenocarcinoma or organ-confined adenocarcinoma. Bioinformatic analysis of the basal cell and two human small cell gene signatures identified a set of E2F target genes common between prostate small cell neuroendocrine carcinoma and primary prostate basal cells. Taken together, our data suggest that aggressive prostate cancer shares a conserved transcriptional program with normal adult prostate basal stem cells.

scholarly journals Characterization of transcriptomic signature of primary prostate cancer analogous to prostatic small cell neuroendocrine carcinoma

2019 ◽  
Vol 145 (12) ◽  
pp. 3453-3461 ◽  
Author(s):  
Mohammed Alshalalfa ◽  
Yang Liu ◽  
Alexander W. Wyatt ◽  
Ewan A. Gibb ◽  
Harrison K. Tsai ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Neuroendocrine Carcinoma ◽  
Small Cell ◽  
Small Cell Neuroendocrine Carcinoma ◽  
Primary Prostate Cancer ◽  
Transcriptomic Signature

scholarly journals Therapy considerations in neuroendocrine prostate cancer: what next?

2021 ◽  
Author(s):  
Himisha Beltran ◽  
Francesca Demichelis
Keyword(s):  
Prostate Cancer ◽  
Treatment Resistance ◽  
Prostate Adenocarcinoma ◽  
Small Cell ◽  
Small Cell Neuroendocrine Carcinoma ◽  
Course Of Disease ◽  
Molecular Features ◽  
Neuroendocrine Prostate Cancer ◽  
Androgen Receptor Activity ◽  
Cancer Phenotype

Lineage plasticity and histologic transformation to small cell neuroendocrine prostate cancer (NEPC) is an increasingly recognized mechanism of treatment resistance in advanced prostate cancer. This is associated with aggressive clinical features and poor prognosis. Recent work has identified genomic, epigenomic, and transcriptome changes that distinguish NEPC from prostate adenocarcinoma, pointing to new mechanisms and therapeutic targets. Treatment-related NEPC arises clonally from prostate adenocarcinoma during the course of disease progression, retaining early genomic events and acquiring new molecular features that lead to tumor proliferation independent of androgen receptor activity, and ultimately demonstrating a lineage switch from a luminal prostate cancer phenotype to a small cell neuroendocrine carcinoma. Identifying the subset of prostate tumors most vulnerable to lineage plasticity and developing strategies for earlier detection and intervention for patients with NEPC may ultimately improve prognosis. Clinical trials focused on drug targeting of the lineage plasticity process and/or NEPC will require careful patient selection. Here, we review emerging targets and discuss biomarker considerations that may be informative for the design of future clinical studies.

scholarly journals Mixed large and small cell neuroendocrine carcinoma and endometrioid carcinoma of the endometrium with high microsatellite instability: A case report and literature review

2021 ◽  
Vol 9 ◽  
pp. 2050313X2199920
Author(s):  
Kotaro Inoue ◽  
Kentaro Kai ◽  
Shimpei Sato ◽  
Haruto Nishida ◽  
Koji Hirakawa ◽  
...  
Keyword(s):  
Microsatellite Instability ◽  
Neuroendocrine Carcinoma ◽  
Immune Checkpoint Blockade ◽  
Japanese Woman ◽  
Endometrial Biopsy ◽  
Small Cell ◽  
Endometrioid Carcinoma ◽  
Small Cell Neuroendocrine Carcinoma ◽  
Mutation Burden ◽  
Solid Part

A 65-year-old, gravida 3, para 2 Japanese woman was referred to our hospital for symptomatic thickening of the endometrial lining. Endocervical and endometrial cytology revealed an adenocarcinoma. The endometrial biopsy specimen was mixed, with a glandular part diagnosed as endometrioid carcinoma and a solid part diagnosed as high-grade mixed large and small cell neuroendocrine carcinoma (L/SCNEC). She underwent extra-fascial hysterectomy with bilateral salpingo-oophorectomy, complete pelvic and para-aortic lymphadenectomy, and omentectomy (FIGO IIIB, pT3b pN0 M0). She currently has no deleterious germline mutation, but high tumor mutation burden and high microsatellite instability (MSI) were identified. She underwent six cycles of platinum-based frontline chemotherapy and achieved complete remission. Immune checkpoint blockade therapy is a promising second-line therapy for MSI-high solid tumors. However, the MSI or mismatch repair (MMR) status of endometrial L/SCNEC remains unclear in the literature. Universal screening for MSI/MMR status is needed, particularly for a rare and aggressive disease.

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