The Rare YAP1 Subtype of SCLC Revisited in a Biobank of 39 Circulating Tumor Cell Patient Derived Explant Models: A Brief Report
| Autor: | Kristopher K. Frese, Derrick Morgan, Sam Humphrey, Mitchell Revill, Kathryn Simpson, Sarah M. Pearsall, Mathew Carter, Caroline Dive, Fiona H Blackhall, Lynsey Priest, Alistair Kerr, Melanie Galvin |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Pulmonary and Respiratory Medicine Lung Neoplasms Cell YAP1 Intratumoral heterogeneity Immunofluorescence 03 medical and health sciences 0302 clinical medicine Circulating tumor cell Cell Line Tumor medicine Humans Transcription factor Adaptor Proteins Signal Transducing Biological Specimen Banks medicine.diagnostic_test business.industry Brief Report YAP-Signaling Proteins Small cell lung cancer (SCLC) Neoplastic Cells Circulating Gene Expression Regulation Neoplastic 030104 developmental biology medicine.anatomical_structure Neuroendocrine Oncology Cell culture 030220 oncology & carcinogenesis NEUROD1 Cancer research Immunohistochemistry business Small Cell Lung Cancer Subtypes Nonneuroendocrine Transcription Factors |
| Zdroj: | Journal of Thoracic Oncology |
| ISSN: | 1556-1380 |
| Popis: | Introduction Recent consensus defines four SCLC subtypes on the basis of transcription factor expression: ASCL1, NEUROD1, POU2F3, and YAP1. The rare YAP1 subtype is associated with “neuroendocrine (NE)-low” cells among SCLC cell lines and patient samples. We evaluated YAP1 in 39 patients with phenotypically diverse circulating tumor cell–derived explant (CDX) models and revisited YAP1 in terms of prevalence, cell phenotype, and intertumor and intratumor heterogeneity. Methods YAP1 transcript and protein expression were assessed by RNA sequencing and immunohistochemistry or multiplexed immunofluorescence of NE and non-NE CDX subpopulations. Physically separated NE and non-NE CDX ex vivo culture lysates were Western blotted for YAP1, NE marker SYP, and AXL. Results RNA sequencing normalized for the four subtype transcription factors identified YAP1 expression in 14 of 39 CDX. A total of 10 CDX expressed YAP1 protein, and eight had strong YAP1 expression confined to rare non-NE cell clusters. This was confirmed in ex vivo CDX cultures in which adherent non-NE cells lacking SYP expression expressed YAP1. However, in two CDX, weaker cellular YAP1 expression was observed, widely dispersed in SYP-positive NE cells. Conclusions YAP1 was predominantly expressed in non-NE cell clusters in SCLC CDX, but two of 39 CDX expressed YAP1 in NE cells. CDX22P, with relatively high YAP1 expression, is an ASCL1 NE subtype with a low NE score and an outlier within this subtype in our CDX biobank. These descriptive data reveal subtly different YAP1 expression profiles, paving the way for functional studies to compare YAP1 signaling in non-NE and low NE cell contexts for potentially personalized therapeutic approaches. |
| Databáze: | OpenAIRE |
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