Combination of tumor asphericity and an extracellular matrix-related prognostic gene signature in non-small cell lung cancer patients

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作者
Sebastian Zschaeck
Bertram Klinger
Jörg van den Hoff
Paulina Cegla
Ivayla Apostolova
Michael C. Kreissl
Witold Cholewiński
Emily Kukuk
Helen Strobel
Holger Amthauer
Nils Blüthgen
Daniel Zips
Frank Hofheinz
机构
[1] Charité-Universitätsmedizin Berlin,Department of Radiation Oncology
[2] Corporate Member of Freie Universität Berlin,Computational Modelling in Medicine, Instiute of Pathology
[3] Humboldt-Universität zu Berlin,Helmholtz
[4] and Berlin Institute of Health,Zentrum Dresden
[5] Berlin Institute of Health (BIH),Rossendorf, PET Center
[6] Charité Universitätsmedizin Berlin,Department of Nuclear Medicine
[7] German Cancer Consortium (DKTK),Department for Diagnostic and Interventional Radiology and Nuclear Medicine
[8] Institute of Radiopharmaceutical Cancer Research,Division of Nuclear Medicine, Department of Radiology and Nuclear Medicine
[9] Greater Poland Cancer Centre,Department of Nuclear Medicine
[10] University Hospital Hamburg-Eppendorf,undefined
[11] Otto Von Guericke University,undefined
[12] Charité-Universitätsmedizin Berlin,undefined
[13] Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin,undefined
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Scientific Reports | / 13卷
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摘要
One important aim of precision oncology is a personalized treatment of patients. This can be achieved by various biomarkers, especially imaging parameters and gene expression signatures are commonly used. So far, combination approaches are sparse. The aim of the study was to independently validate the prognostic value of the novel positron emission tomography (PET) parameter tumor asphericity (ASP) in non small cell lung cancer (NSCLC) patients and to investigate associations between published gene expression profiles and ASP. This was a retrospective evaluation of PET imaging and gene expression data from three public databases and two institutional datasets. The whole cohort comprised 253 NSCLC patients, all treated with curative intent surgery. Clinical parameters, standard PET parameters and ASP were evaluated in all patients. Additional gene expression data were available for 120 patients. Univariate Cox regression and Kaplan–Meier analysis was performed for the primary endpoint progression-free survival (PFS) and additional endpoints. Furthermore, multivariate cox regression testing was performed including clinically significant parameters, ASP, and the extracellular matrix-related prognostic gene signature (EPPI). In the whole cohort, a significant association with PFS was observed for ASP (p < 0.001) and EPPI (p = 0.012). Upon multivariate testing, EPPI remained significantly associated with PFS (p = 0.018) in the subgroup of patients with additional gene expression data, while ASP was significantly associated with PFS in the whole cohort (p = 0.012). In stage II patients, ASP was significantly associated with PFS (p = 0.009), and a previously published cutoff value for ASP (19.5%) was successfully validated (p = 0.008). In patients with additional gene expression data, EPPI showed a significant association with PFS, too (p = 0.033). The exploratory combination of ASP and EPPI showed that the combinatory approach has potential to further improve patient stratification compared to the use of only one parameter. We report the first successful validation of EPPI and ASP in stage II NSCLC patients. The combination of both parameters seems to be a very promising approach for improvement of risk stratification in a group of patients with urgent need for a more personalized treatment approach.
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