Spatial Multiomic Profiling Identifies Metabolic and Inflammatory Signatures Driving Recurrence in Adjuvant-Treated NSCLC Article Swipe

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Arutha Kulasinghe , Naomi Berrell , Chin Wee Tan , A. Kilgallon , James Monkman , Charles Bidgood , Cooper Janke , Meg L. Donovan , Ning Liu , Kidane Siele Embaye , Joseph Yunis , Gwendoline Mendes , Julien Hédou , John F. Fraser , Connor O’Leary , Kenneth J. O’Byrne , Mark N. Adams ·

YOU? · · 2025 · Open Access · · DOI: https://doi.org/10.21203/rs.3.rs-7692105/v1

While there have been therapeutic advancements in treatments for non-small cell lung cancer (NSCLC), we have a limited understanding of how the tumour composition and spatial heterogeneity influences clinical outcomes. Here, we performed a multiomic analysis of 61 NSCLC patients treated with adjuvant chemotherapy and curative resection, integrating spatial transcriptomics, spatial proteomics, and deep learning to profile the tumour microenvironment (TME). We identified spatial-metabolic alterations associated with disease recurrence in and between cells in the TME, involving glutamine import, glycolytic, and lipid oxidation pathways. Based on protein expression, we found spatially distinct regions linked to tumour recurrence, implicating specific roles for tumour associated macrophages, metabolic pathways, and major histocompatibility complex (MHC) proteins. Moreover, transcriptomic analysis revealed histology-specific gene expression changes and metabolic and inflammation pathway associations with tumour recurrence. This comprehensive multiomic analysis highlights the complex immunological and metabolic dynamics characteristic of disease recurrence in adjuvant chemotherapy treated NSCLC.

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Type: article
Landing Page: https://doi.org/10.21203/rs.3.rs-7692105/v1
PDF: https://www.researchsquare.com/article/rs-7692105/latest.pdf
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References: 48
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DOI: https://doi.org/10.21203/rs.3.rs-7692105/v1

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Title: Spatial Multiomic Profiling Identifies Metabolic and Inflammatory Signatures Driving Recurrence in Adjuvant-Treated NSCLC

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Publication year: 2025

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Authors: Arutha Kulasinghe, Naomi Berrell, Chin Wee Tan, A. Kilgallon, James Monkman, Charles Bidgood, Cooper Janke, Meg L. Donovan, Ning Liu, Kidane Siele Embaye, Joseph Yunis, Gwendoline Mendes, Julien Hédou, John F. Fraser, Connor O’Leary, Kenneth J. O’Byrne, Mark N. Adams

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Landing page: https://doi.org/10.21203/rs.3.rs-7692105/v1

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abstract_inverted_index.pathways,	106
abstract_inverted_index.pathways.	84
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abstract_inverted_index.inflammation	124
abstract_inverted_index.macrophages,	104
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abstract_inverted_index.understanding	19
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abstract_inverted_index.microenvironment	60
abstract_inverted_index.transcriptomics,	50
abstract_inverted_index.spatial-metabolic	64
abstract_inverted_index.histocompatibility	109
abstract_inverted_index.histology-specific	117
abstract_inverted_index.<title>Abstract</title>	0
cited_by_percentile_year
countries_distinct_count	2
institutions_distinct_count	17
citation_normalized_percentile.value	0.55508765
citation_normalized_percentile.is_in_top_1_percent	False
citation_normalized_percentile.is_in_top_10_percent	False