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Spatial tumour gene...
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Sallinger, Katja
(författare)
Spatial tumour gene signature discriminates neoplastic from non-neoplastic compartments in colon cancer : unravelling predictive biomarkers for relapse
- Artikel/kapitelEngelska2023
Förlag, utgivningsår, omfång ...
Nummerbeteckningar
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LIBRIS-ID:oai:DiVA.org:su-220913
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https://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-220913URI
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https://doi.org/10.1186/s12967-023-04384-0DOI
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Språk:engelska
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Sammanfattning på:engelska
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Ämneskategori:ref swepub-contenttype
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Ämneskategori:art swepub-publicationtype
Anmärkningar
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Background: Opting for or against the administration of adjuvant chemotherapy in therapeutic management of stage II colon cancer remains challenging. Several studies report few survival benefits for patients treated with adjuvant therapy and additionally revealing potential side effects of overtreatment, including unnecessary exposure to chemotherapy-induced toxicities and reduced quality of life. Predictive biomarkers are urgently needed. We, therefore, hypothesise that the spatial tissue composition of relapsed and non-relapsed colon cancer stage II patients reveals relevant biomarkers.Methods: The spatial tissue composition of stage II colon cancer patients was examined by a novel spatial transcriptomics technology with sub-cellular resolution, namely in situ sequencing. A panel of 176 genes investigating specific cancer-associated processes such as apoptosis, proliferation, angiogenesis, stemness, oxidative stress, hypoxia, invasion and components of the tumour microenvironment was designed to examine differentially expressed genes in tissue of relapsed versus non-relapsed patients. Therefore, FFPE slides of 10 colon cancer stage II patients either classified as relapsed (5 patients) or non-relapsed (5 patients) were in situ sequenced and computationally analysed.Results: We identified a tumour gene signature that enables the subclassification of tissue into neoplastic and non-neoplastic compartments based on spatial expression patterns obtained through in situ sequencing. We developed a computational tool called Genes-To-Count (GTC), which automates the quantification of in situ signals, accurately mapping their position onto the spatial tissue map and automatically identifies neoplastic and non-neoplastic tissue compartments. The GTC tool was used to quantify gene expression of biological processes upregulated within the neoplastic tissue in comparison to non-neoplastic tissue and within relapsed versus non-relapsed stage II colon patients. Three differentially expressed genes (FGFR2, MMP11 and OTOP2) in the neoplastic tissue compartments of relapsed patients in comparison to non-relapsed patients were identified predicting recurrence in stage II colon cancer.Conclusions: In depth spatial in situ sequencing showed potential to provide a deeper understanding of the underlying mechanisms involved in the recurrence of disease and revealed novel potential predictive biomarkers for disease relapse in colon cancer stage II patients. Our open-access GTC-tool allowed us to accurately capture the tumour compartment and quantify spatial gene expression in colon cancer tissue.
Ämnesord och genrebeteckningar
Biuppslag (personer, institutioner, konferenser, titlar ...)
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Gruber, Michael
(författare)
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Mueller, Christin-Therese
(författare)
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Bonstingl, Lilli
(författare)
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Pritz, Elisabeth
(författare)
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Pankratz, Karin
(författare)
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Gerger, Armin
(författare)
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Smolle, Maria Anna
(författare)
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Aigelsreiter, Ariane
(författare)
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Surova, OlgaStockholm Univ, Dept Biochem & Biophys, Sci Life Lab, S-17165 Solna, Sweden
(författare)
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Svedlund, JessicaStockholm Univ, Dept Biochem & Biophys, Sci Life Lab, S-17165 Solna, Sweden
(författare)
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Nilsson, Mats,1969-Stockholms universitet,Institutionen för biokemi och biofysik,Science for Life Laboratory (SciLifeLab)(Swepub:su)matsn
(författare)
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Kroneis, Thomas
(författare)
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El-Heliebi, Amin
(författare)
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Stockholm Univ, Dept Biochem & Biophys, Sci Life Lab, S-17165 Solna, SwedenInstitutionen för biokemi och biofysik
(creator_code:org_t)
Sammanhörande titlar
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Ingår i:Journal of Translational Medicine21:11479-5876
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Sallinger, Katja
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Gruber, Michael
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Mueller, Christi ...
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Bonstingl, Lilli
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Pritz, Elisabeth
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Pankratz, Karin
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visa fler...
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Gerger, Armin
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Smolle, Maria An ...
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Aigelsreiter, Ar ...
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Surova, Olga
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Svedlund, Jessic ...
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Nilsson, Mats, 1 ...
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Kroneis, Thomas
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El-Heliebi, Amin
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visa färre...
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Klinisk medicin
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och Cancer och onkol ...
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Stockholms universitet