Correlation between targeted RNAseq signature of breast cancer CTCs and onset of bone-only metastases

Lovero, Domenica; D’Oronzo, Stella; Palmirotta, Raffaele; Cafforio, Paola; Brown, Janet; Wood, Steven L.; Porta, Camillo; Lauricella, E; Coleman, Robert E.; Silvestris, Franco

doi:10.1038/s41416-021-01481-z

Cited by 11 publications

(7 citation statements)

References 68 publications

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“…Because these outcomes do not measure bone metastasis specifically, we compared the 3-gene signature to an osteotropic breast cancer gene signature ( 28 ). To determine this signature, targeted RNA-Seq was performed on circulating cancer cells of patients with metastatic breast cancer.…”

Section: Resultsmentioning

confidence: 99%

“…Signature correlation was performed on ER + tumors in the TCGA BRCA cohort using a previously published gene set ( 26 , 28 ). TCGA PRAD ( 29 ) data (counts) were downloaded through Xena browser ( 27 ).…”

Section: Methodsmentioning

confidence: 99%

“…FIGURE 2ENTPD1/NT5E/ADORA3 signature is correlated with breast cancer osteotropic signature and lower survival in bone patients with established bone metastases. (A) A previous study(28) found 25 genes to be upregulated in circulating breast cancer cells from patients with bone metastases compared to patients with extraskeletal metastases, forming a putative bone metastasis-specific signature. We compared ENTPD1/NT5E/ADORA3 expression signature to the 25-gene osteotropic signature in the ER + TCGA BRCA cohort.…”

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confidence: 99%

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Association of adenosine signaling gene signature with estrogen receptor-positive breast and prostate cancer bone metastasis

et al. 2022

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Bone metastasis is a common and devastating consequence of several major cancer types, including breast and prostate. Osteocytes are the predominant bone cell, and through connexin (Cx) 43 hemichannels release ATP to the bone microenvironment that can be hydrolyzed to adenosine. Here, we investigated how genes related to ATP paracrine signaling are involved in two common bone-metastasizing malignancies, estrogen receptor positive (ER + ) breast and prostate cancers. Compared to other sites, bone metastases of both cancer types expressed higher levels of ENTPD1 and NT5E, which encode CD39 and CD73, respectively, and hydrolyze ATP to adenosine. ADORA3, encoding the adenosine A3 receptor, had a similar expression pattern. In primary ER + breast cancer, high levels of the triplet ENTPD1/NT5E/ADORA3 expression signature was correlated with lower overall, distant metastasis-free, and progression-free survival. In ER + bone metastasis biopsies, this expression signature is associated with lower survival. This expression signature was also higher in bone-metastasizing primary prostate cancers than in those that caused other tumor events or did not lead to progressive disease. In 3D culture, a non-hydrolyzable ATP analog inhibited the growth of breast and prostate cancer cell lines more than ATP did. A3 inhibition also reduced spheroid growth. Large-scale screens by the Drug Repurposing Hub found ER + breast cancer cell lines were uniquely sensitive Frontiers in Medicine 01 frontiersin.org Shropshire et al. 10.3389/fmed.2022.965429 to adenosine receptor antagonists. Together, these data suggest a vital role for extracellular ATP degradation and adenosine receptor signaling in cancer bone metastasis, and this study provides potential diagnostic means for bone metastasis and specific targets for treatment and prevention.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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confidence: 99%

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Association of adenosine signaling gene signature with estrogen receptor-positive breast and prostate cancer bone metastasis

et al. 2022

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“…2022 ). Lovero et al (2022) recently developed a targeted RNA-sequencing assay including a panel of 134 genes involved in metastasis process in DEPArray-isolated CTCs from stage IV breast cancer but no protocols for 3′ transcriptomic analyses through sequencing starting from DEPArray-isolated cells have been identified so far for gene expression purposes. In this study, we describe a protocol for the 3’ RNA-sequencing of OE33 cells isolated by DEPArray NxT platform as single or pooled cells at different conditions of fixation.…”

Section: Discussionmentioning

confidence: 99%

From phenotypical investigation to RNA-sequencing for gene expression analysis: A workflow for single and pooled rare cells

Rossi

Angeli²,

Martinelli³

et al. 2022

Front. Genet.

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Combining phenotypical and molecular characterization of rare cells is challenging due to their scarcity and difficult handling. In oncology, circulating tumor cells (CTCs) are considered among the most important rare cell populations. Their phenotypic and molecular characterization is necessary to define the molecular mechanisms underlying their metastatic potential. Several approaches that require cell fixation make difficult downstream molecular investigations on RNA. Conversely, the DEPArray technology allows phenotypic analysis and handling of both fixed and unfixed cells, enabling a wider range of applications. Here, we describe an experimental workflow that allows the transcriptomic investigation of single and pooled OE33 cells undergone to DEPArray analysis and recovery. In addition, cells were tested at different conditions (unfixed, CellSearch fixative (CSF)- and ethanol (EtOH)-fixed cells). In a forward-looking perspective, this workflow will pave the way for novel strategies to characterize gene expression profiles of rare cells, both single-cell and low-resolution input.

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“…Because of genome plasticity, cfDNA might not be fully informed of cancer evolution, representing an average of multiple subclones present in the individual patient, providing the rationale for the search for alternative non-invasive and not-expensive platforms. In this context, microfluidic single-cell manipulation [ 104 ] for enumeration and isolation of CTCs is by far the best biological matrices to move from single gene analysis to single-cell profiling that is required for the new era of precision medicine [ 104 , 105 , 106 ].…”

Section: The Role Of Ctcs In Precision Medicinementioning

confidence: 99%

The Role of Dielectrophoresis for Cancer Diagnosis and Prognosis

Russo

Musso

Romano

et al. 2021

Cancers

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Liquid biopsy is emerging as a potential diagnostic tool for prostate cancer (PC) prognosis and diagnosis. Unfortunately, most circulating tumor cells (CTC) technologies, such as AdnaTest or Cellsearch®, critically rely on the epithelial cell adhesion molecule (EpCAM) marker, limiting the possibility of detecting cancer stem-like cells (CSCs) and mesenchymal-like cells (EMT-CTCs) that are present during PC progression. In this context, dielectrophoresis (DEP) is an epCAM independent, label-free enrichment system that separates rare cells simply on the basis of their specific electrical properties. As compared to other technologies, DEP may represent a superior technique in terms of running costs, cell yield and specificity. However, because of its higher complexity, it still requires further technical as well as clinical development. DEP can be improved by the use of microfluid, nanostructured materials and fluoro-imaging to increase its potential applications. In the context of cancer, the usefulness of DEP lies in its capacity to detect CTCs in the bloodstream in their epithelial, mesenchymal, or epithelial–mesenchymal phenotype forms, which should be taken into account when choosing CTC enrichment and analysis methods for PC prognosis and diagnosis.

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Correlation between targeted RNAseq signature of breast cancer CTCs and onset of bone-only metastases

Cited by 11 publications

References 68 publications

Association of adenosine signaling gene signature with estrogen receptor-positive breast and prostate cancer bone metastasis

Association of adenosine signaling gene signature with estrogen receptor-positive breast and prostate cancer bone metastasis

From phenotypical investigation to RNA-sequencing for gene expression analysis: A workflow for single and pooled rare cells

The Role of Dielectrophoresis for Cancer Diagnosis and Prognosis

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