Glioblastoma is an aggressive brain tumor with an average life expectancy between 14 and 16 months after diagnosis. The Ki-67 labeling index (LI), a measure of cellular proliferation, is emerging as a prognostic marker in GBM. In this study, we investigated the ultrastructure of glioblastoma tissue from 9 patients with the same molecular profile (adult IDH wild-type glioblastoma, wild-type ATRX, and positive for TP53 expression, GFAP expression, and EGFR overexpression) to find possible ultrastructural features to be used as biomarkers and correlated with the only parameter that differs among our samples, the Ki-67 LI. Our main results were the visualization of the anatomical basis of astrocyte-endothelial cells crosstalk; the ultrastructural in situ imaging of clusters of hyperactivated microglia cells (MsEVs); the ultrastructural in situ imaging of microglia cells storing lipid vesicles (MsLVs); the ultrastructural in situ imaging of neoplastic cells mitophagy (NCsM). The statistical analysis of our data indicated that MsEVs and MsLVs correlate with the Ki-67 LI value. We can thus assume they are good candidates to be considered morphological biomarkers correlating to Ki-67 LI. The role of NCsM instead must be further evaluated. Our study findings demonstrate that by combining ultrastructural characteristics with molecular information, we can discover biomarkers that have the potential to enhance diagnostic precision, aid in treatment decision-making, identify targets for therapy, and enable personalized treatment plans tailored to each patient. However, further research with larger sample sizes is needed to validate these findings and fully utilize the potential of ultrastructural analysis in managing glioblastoma.

Adult IDH wild-type glioblastoma ultrastructural investigation suggests a possible correlation between morphological biomarkers and Ki-67 index / Familiari, Pietro; Relucenti, Michela; Lapolla, Pierfrancesco; Palmieri, Mauro; Antonelli, Manila; Cristiano, Loredana; Barbaranelli, Claudio; Catalano, Myriam; D’Angelo, Luca; Familiari, Giuseppe; Santoro, Antonio; Frati, Alessandro; Bruzzaniti, Placido. - In: BIOMEDICINES. - ISSN 2227-9059. - 11:7(2023). [10.3390/biomedicines11071968]

Adult IDH wild-type glioblastoma ultrastructural investigation suggests a possible correlation between morphological biomarkers and Ki-67 index

Pietro Familiari
Co-primo
;
Michela Relucenti
Co-primo
;
Pierfrancesco Lapolla
Secondo
;
Mauro Palmieri;Manila Antonelli;Claudio Barbaranelli;Myriam Catalano;Giuseppe Familiari;Antonio Santoro;Alessandro Frati
Penultimo
;
Placido Bruzzaniti
Ultimo
2023

Abstract

Glioblastoma is an aggressive brain tumor with an average life expectancy between 14 and 16 months after diagnosis. The Ki-67 labeling index (LI), a measure of cellular proliferation, is emerging as a prognostic marker in GBM. In this study, we investigated the ultrastructure of glioblastoma tissue from 9 patients with the same molecular profile (adult IDH wild-type glioblastoma, wild-type ATRX, and positive for TP53 expression, GFAP expression, and EGFR overexpression) to find possible ultrastructural features to be used as biomarkers and correlated with the only parameter that differs among our samples, the Ki-67 LI. Our main results were the visualization of the anatomical basis of astrocyte-endothelial cells crosstalk; the ultrastructural in situ imaging of clusters of hyperactivated microglia cells (MsEVs); the ultrastructural in situ imaging of microglia cells storing lipid vesicles (MsLVs); the ultrastructural in situ imaging of neoplastic cells mitophagy (NCsM). The statistical analysis of our data indicated that MsEVs and MsLVs correlate with the Ki-67 LI value. We can thus assume they are good candidates to be considered morphological biomarkers correlating to Ki-67 LI. The role of NCsM instead must be further evaluated. Our study findings demonstrate that by combining ultrastructural characteristics with molecular information, we can discover biomarkers that have the potential to enhance diagnostic precision, aid in treatment decision-making, identify targets for therapy, and enable personalized treatment plans tailored to each patient. However, further research with larger sample sizes is needed to validate these findings and fully utilize the potential of ultrastructural analysis in managing glioblastoma.
2023
EVs; Ki67; biomarker; glioblastoma; lipid vesicles; microglia
01 Pubblicazione su rivista::01a Articolo in rivista
Adult IDH wild-type glioblastoma ultrastructural investigation suggests a possible correlation between morphological biomarkers and Ki-67 index / Familiari, Pietro; Relucenti, Michela; Lapolla, Pierfrancesco; Palmieri, Mauro; Antonelli, Manila; Cristiano, Loredana; Barbaranelli, Claudio; Catalano, Myriam; D’Angelo, Luca; Familiari, Giuseppe; Santoro, Antonio; Frati, Alessandro; Bruzzaniti, Placido. - In: BIOMEDICINES. - ISSN 2227-9059. - 11:7(2023). [10.3390/biomedicines11071968]
File allegati a questo prodotto
File Dimensione Formato  
Familiari_Adult IDH_2023.pdf

accesso aperto

Tipologia: Versione editoriale (versione pubblicata con il layout dell'editore)
Licenza: Creative commons
Dimensione 6.89 MB
Formato Adobe PDF
6.89 MB Adobe PDF

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1686893
Citazioni
  • ???jsp.display-item.citation.pmc??? 2
  • Scopus 2
  • ???jsp.display-item.citation.isi??? 2
social impact