High-Plex and High-Throughput Digital Spatial Profiling of Non-Small-Cell Lung Cancer (NSCLC).

Monkman, J; Taheri, T; Ebrahimi Warkiani, M; O'Leary, C; Ladwa, R; Richard, D; O'Byrne, K; Kulasinghe, A

High-Plex and High-Throughput Digital Spatial Profiling of Non-Small-Cell Lung Cancer (NSCLC).

Monkman, J Taheri, T Ebrahimi Warkiani, M

O'Leary, C Ladwa, R Richard, D O'Byrne, K Kulasinghe, A

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Publisher:: MDPI AG
Publication Type:: Journal Article
Citation:: Cancers, 2020, 12, (12), pp. 1-14
Issue Date:: 2020-11-27

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Field	Value	Language
dc.contributor.author	Monkman, J
dc.contributor.author	Taheri, T
dc.contributor.author	Ebrahimi Warkiani, M https://orcid.org/0000-0002-4184-1944
dc.contributor.author	O'Leary, C
dc.contributor.author	Ladwa, R
dc.contributor.author	Richard, D
dc.contributor.author	O'Byrne, K
dc.contributor.author	Kulasinghe, A
dc.date.accessioned	2021-03-19T08:36:35Z
dc.date.available	2020-11-25
dc.date.available	2021-03-19T08:36:35Z
dc.date.issued	2020-11-27
dc.identifier.citation	Cancers, 2020, 12, (12), pp. 1-14
dc.identifier.issn	2072-6694
dc.identifier.issn	2072-6694
dc.identifier.uri	http://hdl.handle.net/10453/147390
dc.description.abstract	Profiling the tumour microenvironment (TME) has been informative in understanding the underlying tumour-immune interactions. Multiplex immunohistochemistry (mIHC) coupled with molecular barcoding technologies have revealed greater insights into the TME. In this study, we utilised the Nanostring GeoMX Digital Spatial Profiler (DSP) platform to profile a non-small-cell lung cancer (NSCLC) tissue microarray for protein markers across immune cell profiling, immuno-oncology (IO) drug targets, immune activation status, immune cell typing, and pan-tumour protein modules. Regions of interest (ROIs) were selected that described tumour, TME, and normal adjacent tissue (NAT) compartments. Our data revealed that paired analysis (<i>n</i> = 18) of matched patient compartments indicate that the TME was significantly enriched in CD27, CD3, CD4, CD44, CD45, CD45RO, CD68, CD163, and VISTA relative to the tumour. Unmatched analysis indicated that the NAT (<i>n</i> = 19) was significantly enriched in CD34, fibronectin, IDO1, LAG3, ARG1, and PTEN when compared to the TME (<i>n</i> = 32). Univariate Cox proportional hazards indicated that the presence of cells expressing CD3 (hazard ratio (HR): 0.5, <i>p</i> = 0.018), CD34 (HR: 0.53, <i>p</i> = 0.004), and ICOS (HR: 0.6, <i>p</i> = 0.047) in tumour compartments were significantly associated with improved overall survival (OS). We implemented both high-plex and high-throughput methodologies to the discovery of protein biomarkers and molecular phenotypes within biopsy samples, and demonstrate the power of such tools for a new generation of pathology research.
dc.format	Electronic
dc.language	eng
dc.publisher	MDPI AG
dc.relation.ispartof	Cancers
dc.relation.isbasedon	10.3390/cancers12123551
dc.rights	info:eu-repo/semantics/openAccess
dc.subject	1112 Oncology and Carcinogenesis
dc.title	High-Plex and High-Throughput Digital Spatial Profiling of Non-Small-Cell Lung Cancer (NSCLC).
dc.type	Journal Article
utslib.citation.volume	12
utslib.location.activity	Switzerland
utslib.for	1112 Oncology and Carcinogenesis
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Engineering and Information Technology
pubs.organisational-group	/University of Technology Sydney/Strength - CHT - Health Technologies
pubs.organisational-group	/University of Technology Sydney/Faculty of Engineering and Information Technology/School of Biomedical Engineering
pubs.organisational-group	/University of Technology Sydney/Strength - IBMD - Initiative for Biomedical Devices
utslib.copyright.status	open_access	*
dc.date.updated	2021-03-19T08:36:28Z
pubs.issue	12
pubs.publication-status	Published
pubs.volume	12
utslib.citation.issue	12

Abstract:

Profiling the tumour microenvironment (TME) has been informative in understanding the underlying tumour-immune interactions. Multiplex immunohistochemistry (mIHC) coupled with molecular barcoding technologies have revealed greater insights into the TME. In this study, we utilised the Nanostring GeoMX Digital Spatial Profiler (DSP) platform to profile a non-small-cell lung cancer (NSCLC) tissue microarray for protein markers across immune cell profiling, immuno-oncology (IO) drug targets, immune activation status, immune cell typing, and pan-tumour protein modules. Regions of interest (ROIs) were selected that described tumour, TME, and normal adjacent tissue (NAT) compartments. Our data revealed that paired analysis (n = 18) of matched patient compartments indicate that the TME was significantly enriched in CD27, CD3, CD4, CD44, CD45, CD45RO, CD68, CD163, and VISTA relative to the tumour. Unmatched analysis indicated that the NAT (n = 19) was significantly enriched in CD34, fibronectin, IDO1, LAG3, ARG1, and PTEN when compared to the TME (n = 32). Univariate Cox proportional hazards indicated that the presence of cells expressing CD3 (hazard ratio (HR): 0.5, p = 0.018), CD34 (HR: 0.53, p = 0.004), and ICOS (HR: 0.6, p = 0.047) in tumour compartments were significantly associated with improved overall survival (OS). We implemented both high-plex and high-throughput methodologies to the discovery of protein biomarkers and molecular phenotypes within biopsy samples, and demonstrate the power of such tools for a new generation of pathology research.

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http://hdl.handle.net/10453/147390