Combination of tumor asphericity and an extracellular matrix-related prognostic gene signature in non-small cell lung cancer patients
Abstract 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 v...
| Автори: | , , , , , , , , , , , , |
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| Формат: | Стаття |
| Мова: | English |
| Опубліковано: |
Nature Portfolio
2023-11-01
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| Серія: | Scientific Reports |
| Онлайн доступ: | https://doi.org/10.1038/s41598-023-46405-4 |
| _version_ | 1827603816316403712 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Sebastian Zschaeck |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-03-09T05:47:02Z |
| format | Article |
| id | doaj.art-51a246b6af664a0f8c1a1cf18b1d9d3f |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-03-09T05:47:02Z |
| publishDate | 2023-11-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-51a246b6af664a0f8c1a1cf18b1d9d3f2023-12-03T12:19:51ZengNature PortfolioScientific Reports2045-23222023-11-0113111110.1038/s41598-023-46405-4Combination of tumor asphericity and an extracellular matrix-related prognostic gene signature in non-small cell lung cancer patientsSebastian Zschaeck0Bertram Klinger1Jörg van den Hoff2Paulina Cegla3Ivayla Apostolova4Michael C. Kreissl5Witold Cholewiński6Emily Kukuk7Helen Strobel8Holger Amthauer9Nils Blüthgen10Daniel Zips11Frank Hofheinz12Department of Radiation Oncology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of HealthBerlin Institute of Health (BIH)Helmholtz-Zentrum Dresden-Rossendorf, PET Center, Institute of Radiopharmaceutical Cancer ResearchDepartment of Nuclear Medicine, Greater Poland Cancer CentreDepartment for Diagnostic and Interventional Radiology and Nuclear Medicine, University Hospital Hamburg-EppendorfDivision of Nuclear Medicine, Department of Radiology and Nuclear Medicine, Otto Von Guericke UniversityDepartment of Nuclear Medicine, Greater Poland Cancer CentreDepartment of Radiation Oncology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of HealthDepartment of Radiation Oncology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of HealthDivision of Nuclear Medicine, Department of Radiology and Nuclear Medicine, Otto Von Guericke UniversityBerlin Institute of Health (BIH)Department of Radiation Oncology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of HealthHelmholtz-Zentrum Dresden-Rossendorf, PET Center, Institute of Radiopharmaceutical Cancer ResearchAbstract 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.https://doi.org/10.1038/s41598-023-46405-4 |
| spellingShingle | 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 Combination of tumor asphericity and an extracellular matrix-related prognostic gene signature in non-small cell lung cancer patients Scientific Reports |
| title | Combination of tumor asphericity and an extracellular matrix-related prognostic gene signature in non-small cell lung cancer patients |
| title_full | Combination of tumor asphericity and an extracellular matrix-related prognostic gene signature in non-small cell lung cancer patients |
| title_fullStr | Combination of tumor asphericity and an extracellular matrix-related prognostic gene signature in non-small cell lung cancer patients |
| title_full_unstemmed | Combination of tumor asphericity and an extracellular matrix-related prognostic gene signature in non-small cell lung cancer patients |
| title_short | Combination of tumor asphericity and an extracellular matrix-related prognostic gene signature in non-small cell lung cancer patients |
| title_sort | combination of tumor asphericity and an extracellular matrix related prognostic gene signature in non small cell lung cancer patients |
| url | https://doi.org/10.1038/s41598-023-46405-4 |
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