| Creators: |
Prokop, Georg and Wiestler, Benedikt and Hieber, Daniel and Withake, Fynn and Mayer, Karoline and Gempt, Jens and Delbridge, Claire and Schmidt-Graf, Friederike and Pfarr, Nicole and Märkl, Bruno and Schlegel, Jürgen and Liesche-Starnecker, Friederike |
| Title: |
Multiscale quantification of morphological heterogeneity with creation of a predictor of longer survival in glioblastoma |
| Item Type: |
Article or issue of a publication series |
| Projects: |
DigiHealth, NAP |
| Journal or Series Title: |
International Journal of Cancer |
| Additional Information: |
Open Access: CC-BY-NC 4.0 |
| Date: |
July 2023 |
| Divisions: |
Gesundheitsmanagement |
| Abstract (ENG): |
Intratumor heterogeneity is a main cause of the dismal prognosis of glioblastoma (GBM). Yet, there remains a lack of a uniform assessment of the degree of heterogeneity. With a multiscale approach, we addressed the hypothesis that intratumor heterogeneity exists on different levels comprising traditional regional analyses, but also innovative methods including computer-assisted analysis of tumor morphology combined with epigenomic data. With this aim, 157 biopsies of 37 patients with therapy-naive IDH-wildtype GBM were analyzed regarding the intratumor variance of protein expression of glial marker GFAP, microglia marker Iba1 and proliferation marker Mib1. Hematoxylin and eosin stained slides were evaluated for tumor vascularization. For the estimation of pixel intensity and nuclear profiling, automated analysis was used. Additionally, DNA methylation profiling was conducted separately for the single biopsies. Scoring systems were established to integrate several parameters into one score for the four examined modalities of heterogeneity (regional, cellular, pixel-level and epigenomic). As a result, we could show that heterogeneity was detected in all four modalities. Furthermore, for the regional, cellular and epigenomic level, we confirmed the results of earlier studies stating that a higher degree of heterogeneity is associated with poorer overall survival. To integrate all modalities into one score, we designed a predictor of longer survival, which showed a highly significant separation regarding the OS. In conclusion, multiscale intratumor heterogeneity exists in glioblastoma and its degree has an impact on overall survival. In future studies, the implementation of a broadly feasible heterogeneity index should be considered. |
| Forthcoming: |
No |
| Language: |
English |
| Link eMedia: |
Download |
| Citation: |
Prokop, Georg and Wiestler, Benedikt and Hieber, Daniel and Withake, Fynn and Mayer, Karoline and Gempt, Jens and Delbridge, Claire and Schmidt-Graf, Friederike and Pfarr, Nicole and Märkl, Bruno and Schlegel, Jürgen and Liesche-Starnecker, Friederike
(2023)
Multiscale quantification of morphological heterogeneity with creation of a predictor of longer survival in glioblastoma.
International Journal of Cancer.
ISSN 1097-0215
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