Identification of Spatial Proteomic Signatures of Colon Tumor Metastasis: A Digital Spatial Profiling Approach Article Swipe
Joshua Levy
,
John P. Zavras
,
Eren M. Veziroglu
,
Mustafa Nasir-Moin
,
Fred Kolling
,
Brock C. Christensen
,
Lucas A. Salas
,
Rachael E. Barney
,
Scott Palisoul
,
Bing Ren
,
Xiaoying Liu
,
Darcy A. Kerr
,
Kelli B. Pointer
,
Gregory J. Tsongalis
,
Louis Vaickus
·
YOU?
·
· 2022
· Open Access
·
· DOI: https://doi.org/10.1101/2022.12.04.22283073
YOU?
·
· 2022
· Open Access
·
· DOI: https://doi.org/10.1101/2022.12.04.22283073
Over 150,000 Americans are diagnosed with colorectal cancer (CRC) every year, and annually over 50,000 individuals will die from CRC, necessitating improvements in screening, prognostication, disease management, and therapeutic options. CRC tumors are removed en bloc with surrounding vasculature and lymphatics. Examination of regional lymph nodes at the time of surgical resection is essential for prognostication. Developing alternative approaches to indirectly assess recurrence risk would have utility in cases where lymph node yield is incomplete or inadequate. Spatially dependent, immune cell-specific (e.g., Tumor Infiltrating Lymphocytes– TILs), proteomic, and transcriptomic expression patterns inside and around the tumor - the tumor immune microenvironment (TIME) - can predict nodal/distant metastasis and probe the coordinated immune response from the primary tumor site. The comprehensive characterization of TILs and other immune infiltrates is possible using highly multiplexed spatial omics technologies, such as the GeoMX Digital Spatial Profiler (DSP). In this study, machine learning and differential co-expression analyses helped identify biomarkers from DSP-assayed protein expression patterns inside, at the invasive margin, and away from the tumor, associated with extracellular matrix remodeling (e.g., GZMB, fibronectin), immune suppression (e.g., FOXP3), exhaustion and cytotoxicity (e.g., CD8), PD-L1 expressing dendritic cells, neutrophil proliferation, amongst other concomitant alterations. Further investigation of these biomarkers may reveal independent risk factors of CRC metastasis that can be formulated into low-cost, widely available assays.
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Metadata
- Type
- preprint
- Language
- en
- Landing Page
- https://doi.org/10.1101/2022.12.04.22283073
- https://www.medrxiv.org/content/medrxiv/early/2022/12/06/2022.12.04.22283073.full.pdf
- OA Status
- green
- Cited By
- 2
- References
- 67
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4311652140
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4311652140Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.1101/2022.12.04.22283073Digital Object Identifier
- Title
-
Identification of Spatial Proteomic Signatures of Colon Tumor Metastasis: A Digital Spatial Profiling ApproachWork title
- Type
-
preprintOpenAlex work type
- Language
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enPrimary language
- Publication year
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2022Year of publication
- Publication date
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2022-12-06Full publication date if available
- Authors
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Joshua Levy, John P. Zavras, Eren M. Veziroglu, Mustafa Nasir-Moin, Fred Kolling, Brock C. Christensen, Lucas A. Salas, Rachael E. Barney, Scott Palisoul, Bing Ren, Xiaoying Liu, Darcy A. Kerr, Kelli B. Pointer, Gregory J. Tsongalis, Louis VaickusList of authors in order
- Landing page
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https://doi.org/10.1101/2022.12.04.22283073Publisher landing page
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https://www.medrxiv.org/content/medrxiv/early/2022/12/06/2022.12.04.22283073.full.pdfDirect link to full text PDF
- Open access
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YesWhether a free full text is available
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greenOpen access status per OpenAlex
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https://www.medrxiv.org/content/medrxiv/early/2022/12/06/2022.12.04.22283073.full.pdfDirect OA link when available
- Concepts
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Immune system, FOXP3, Tumor microenvironment, Metastasis, Colorectal cancer, Cancer research, Medicine, Primary tumor, CD8, Immunology, Oncology, Cancer, Internal medicineTop concepts (fields/topics) attached by OpenAlex
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2Total citation count in OpenAlex
- Citations by year (recent)
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2023: 2Per-year citation counts (last 5 years)
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67Number of works referenced by this work
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10Other works algorithmically related by OpenAlex
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| abstract_inverted_index.diagnosed | 5 |
| abstract_inverted_index.essential | 54 |
| abstract_inverted_index.low-cost, | 216 |
| abstract_inverted_index.resection | 52 |
| abstract_inverted_index.Developing | 57 |
| abstract_inverted_index.approaches | 59 |
| abstract_inverted_index.associated | 171 |
| abstract_inverted_index.biomarkers | 155, 202 |
| abstract_inverted_index.colorectal | 7 |
| abstract_inverted_index.dependent, | 79 |
| abstract_inverted_index.exhaustion | 183 |
| abstract_inverted_index.expressing | 189 |
| abstract_inverted_index.expression | 90, 159 |
| abstract_inverted_index.formulated | 214 |
| abstract_inverted_index.incomplete | 75 |
| abstract_inverted_index.indirectly | 61 |
| abstract_inverted_index.metastasis | 107, 210 |
| abstract_inverted_index.neutrophil | 192 |
| abstract_inverted_index.proteomic, | 87 |
| abstract_inverted_index.recurrence | 63 |
| abstract_inverted_index.remodeling | 175 |
| abstract_inverted_index.screening, | 24 |
| abstract_inverted_index.DSP-assayed | 157 |
| abstract_inverted_index.Examination | 42 |
| abstract_inverted_index.alternative | 58 |
| abstract_inverted_index.concomitant | 196 |
| abstract_inverted_index.coordinated | 111 |
| abstract_inverted_index.inadequate. | 77 |
| abstract_inverted_index.independent | 205 |
| abstract_inverted_index.individuals | 16 |
| abstract_inverted_index.infiltrates | 127 |
| abstract_inverted_index.lymphatics. | 41 |
| abstract_inverted_index.management, | 27 |
| abstract_inverted_index.multiplexed | 132 |
| abstract_inverted_index.suppression | 180 |
| abstract_inverted_index.surrounding | 38 |
| abstract_inverted_index.therapeutic | 29 |
| abstract_inverted_index.vasculature | 39 |
| abstract_inverted_index.Infiltrating | 84 |
| abstract_inverted_index.alterations. | 197 |
| abstract_inverted_index.cytotoxicity | 185 |
| abstract_inverted_index.differential | 150 |
| abstract_inverted_index.improvements | 22 |
| abstract_inverted_index.cell-specific | 81 |
| abstract_inverted_index.co-expression | 151 |
| abstract_inverted_index.comprehensive | 120 |
| abstract_inverted_index.extracellular | 173 |
| abstract_inverted_index.fibronectin), | 178 |
| abstract_inverted_index.investigation | 199 |
| abstract_inverted_index.necessitating | 21 |
| abstract_inverted_index.nodal/distant | 106 |
| abstract_inverted_index.technologies, | 135 |
| abstract_inverted_index.Lymphocytes– | 85 |
| abstract_inverted_index.proliferation, | 193 |
| abstract_inverted_index.transcriptomic | 89 |
| abstract_inverted_index.characterization | 121 |
| abstract_inverted_index.microenvironment | 101 |
| abstract_inverted_index.prognostication, | 25 |
| abstract_inverted_index.prognostication. | 56 |
| cited_by_percentile_year.max | 96 |
| cited_by_percentile_year.min | 94 |
| corresponding_author_ids | https://openalex.org/A5053202754 |
| countries_distinct_count | 1 |
| institutions_distinct_count | 15 |
| corresponding_institution_ids | https://openalex.org/I107672454, https://openalex.org/I126688049, https://openalex.org/I4390039337 |
| sustainable_development_goals[0].id | https://metadata.un.org/sdg/3 |
| sustainable_development_goals[0].score | 0.4300000071525574 |
| sustainable_development_goals[0].display_name | Good health and well-being |
| citation_normalized_percentile.value | 0.57538927 |
| citation_normalized_percentile.is_in_top_1_percent | False |
| citation_normalized_percentile.is_in_top_10_percent | False |