Stroma AReactive Invasion Front Areas (SARIFA) proves prognostic relevance in gastric carcinoma and is based on a tumor–adipocyte interaction indicating an altered immune response

  • Background Recently, we presented Stroma AReactive Invasion Front Areas (SARIFA) as a new histomorphologic negative prognostic biomarker in gastric cancer. It is defined as direct contact between tumor cells and fat cells. The aim of this study was to further elucidate the underlying genomic, transcriptional, and immunological mechanisms of the SARIFA phenomenon. Methods To address these questions, SARIFA was classified on H&E-stained tissue sections of three cohorts: an external cohort (n = 489, prognostic validation), the TCGA-STAD cohort (n = 194, genomic and transcriptomic analysis), and a local cohort (n = 60, digital spatial profiling (whole transcriptome) and double RNA in situ hybridization/immunostaining of cytokines). Results SARIFA status proved to be an independent negative prognostic factor for overall survival in an external cohort of gastric carcinomas. In TCGA-STAD cohort, SARIFA is not driven by distinct genomic alterations, whereas the gene expressionBackground Recently, we presented Stroma AReactive Invasion Front Areas (SARIFA) as a new histomorphologic negative prognostic biomarker in gastric cancer. It is defined as direct contact between tumor cells and fat cells. The aim of this study was to further elucidate the underlying genomic, transcriptional, and immunological mechanisms of the SARIFA phenomenon. Methods To address these questions, SARIFA was classified on H&E-stained tissue sections of three cohorts: an external cohort (n = 489, prognostic validation), the TCGA-STAD cohort (n = 194, genomic and transcriptomic analysis), and a local cohort (n = 60, digital spatial profiling (whole transcriptome) and double RNA in situ hybridization/immunostaining of cytokines). Results SARIFA status proved to be an independent negative prognostic factor for overall survival in an external cohort of gastric carcinomas. In TCGA-STAD cohort, SARIFA is not driven by distinct genomic alterations, whereas the gene expression analyses showed an upregulation of FABP4 in SARIFA-positive tumors. In addition, the transcriptional regulations of white adipocyte differentiation, triglyceride metabolism, and catabolism were upregulated in pathway analyses. In the DSP analysis of SARIFA-positive tumors, FABP4 and the transcriptional regulation of white adipocyte differentiation were upregulated in macrophages. Additionally, a significantly lower expression of the cytokines IL6 and TNFα was observed at the invasion front. Conclusions SARIFA proves to be a strong negative prognostic biomarker in advanced gastric cancer, implicating an interaction of tumor cells with tumor-promoting adipocytes with crucial changes in tumor cell metabolism. SARIFA is not driven by tumor genetics but is very likely driven by an altered immune response as a causative mechanism.show moreshow less

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Author:Bianca Grosser, Christian M. HeyerORCiDGND, Johannes Austgen, Eva Sipos, Nic G. Reitsam, Andreas Hauser, Alison VanSchoiack, David Kroeppler, Dmytro Vlasenko, Andreas Probst, Alexander Novotny, Wilko Weichert, Gisela Keller, Matthias SchlesnerORCiDGND, Bruno MärklORCiDGND
URN:urn:nbn:de:bvb:384-opus4-1091068
Frontdoor URLhttps://opus.bibliothek.uni-augsburg.de/opus4/109106
ISSN:1436-3291OPAC
ISSN:1436-3305OPAC
Parent Title (English):Gastric Cancer
Publisher:Springer Science and Business Media LLC
Type:Article
Language:English
Date of first Publication:2023/10/24
Publishing Institution:Universität Augsburg
Release Date:2023/11/13
Tag:Cancer Research; Gastroenterology; Oncology; General Medicine
Volume:27
First Page:72
Last Page:85
DOI:https://doi.org/10.1007/s10120-023-01436-8
Institutes:Fakultät für Angewandte Informatik
Fakultät für Angewandte Informatik / Institut für Informatik
Medizinische Fakultät
Fakultät für Angewandte Informatik / Institut für Informatik / Lehrstuhl für Biomedizinische Informatik, Data Mining und Data Analytics
Medizinische Fakultät / Universitätsklinikum
Medizinische Fakultät / Lehrstuhl für Allgemeine und Spezielle Pathologie
Medizinische Fakultät / Lehrstuhl für Innere Medizin mit Schwerpunkt Gastroenterologie
Medizinische Fakultät / Lehrstuhl für Allgemein- und Viszeralchirurgie
Nachhaltigkeitsziele
Nachhaltigkeitsziele / Ziel 3 - Gesundheit und Wohlergehen
Dewey Decimal Classification:0 Informatik, Informationswissenschaft, allgemeine Werke / 00 Informatik, Wissen, Systeme / 004 Datenverarbeitung; Informatik
6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Licence (German):CC-BY 4.0: Creative Commons: Namensnennung (mit Print on Demand)