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. 2024 Mar 29;13(7):597.
doi: 10.3390/cells13070597.

CD99 Expression and Prognostic Impact in Glioblastoma: A Single-Center Cohort Study

Andrea Rocca  1 , Fabiola Giudici  2 , Carmine Antonio Donofrio  3   4 , Cristina Bottin  1 , Maurizio Pinamonti  1 , Benvenuto Ferrari  5 , Francesco Schettini  6   7   8 , Estela Pineda  7   8 , Stefano Panni  5 , Marika Cominetti  3 , Patrizia D'Auria  3 , Simonetta Bianchini  3 , Elena Varotti  9 , Marco Ungari  9 , Stefano Ciccarelli  10 , Marzia Filippini  10 , Sarah Brenna  10 , Valentina Fiori  11 , Tomas Di Mambro  11 , Angelo Sparti  12 , Mauro Magnani  12 , Fabrizio Zanconati  1 , Daniele Generali  1   5 , Antonio Fioravanti  3
Affiliations

CD99 Expression and Prognostic Impact in Glioblastoma: A Single-Center Cohort Study

Andrea Rocca et al. Cells. .

Abstract

Glioblastoma is the most frequent and aggressive brain tumor in adults. This study aims to evaluate the expression and prognostic impact of CD99, a membrane glycoprotein involved in cellular migration and invasion. In a cohort of patients with glioblastoma treated with surgery, radiotherapy and temozolomide, we retrospectively analyzed tumor expression of CD99 by immunohistochemistry (IHC) and by quantitative real-time polymerase chain reaction (qRT-PCR) for both the wild type (CD99wt) and the truncated (CD99sh) isoforms. The impact on overall survival (OS) was assessed with the Kaplan-Meier method and log-rank test and by multivariable Cox regression. Forty-six patients with glioblastoma entered this study. Immunohistochemical expression of CD99 was present in 83%. Only the CD99wt isoform was detected by qRT-PCR and was significantly correlated with CD99 expression evaluated by IHC (rho = 0.309, p = 0.037). CD99 expression was not associated with OS, regardless of the assessment methodology used (p = 0.61 for qRT-PCR and p = 0.73 for IHC). In an exploratory analysis of The Cancer Genome Atlas, casuistry of glioblastomas CD99 expression was not associated with OS nor with progression-free survival. This study confirms a high expression of CD99 in glioblastoma but does not show any significant impact on survival. Further preclinical studies are needed to define its role as a therapeutic target in glioblastoma.

Keywords: CD99; glioblastoma; immunohistochemistry; prognostic factor; quantitative real-time polymerase chain reaction.

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Conflict of interest statement

V.F. and T.D.M. are employees of Diatheva srl. The other authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Immunohistochemical staining for CD99. All expression classes of CD99 are represented: 0, 1+, 2+ (both a positive and a negative area from the same sample), 3+. Original magnification 20×.
Figure 2
Figure 2
Correlation of quantitative real-time polymerase chain reaction analyses for CD99 with semi-quantitative immunohistochemistry. IHC: immunohistochemistry; qRT-PCR: quantitative real-time reverse transcriptase polymerase chain reaction.
Figure 3
Figure 3
Overall survival according to CD99 status by quantitative real-time polymerase chain reaction analyses and immunohistochemistry. (A) Overall survival by CD99 qRT-PCR expression; (B) overall survival by CD99 IHC expression, considering two levels (0/1+ vs. 2+/3+); (C) overall survival by CD99 IHC expression, considering three levels (0 vs. 1+/2+ vs. 3+); (D) overall survival by CD99 IHC expression, considering four levels (0 vs. 1+ vs. 2+ vs. 3+). qRT-PCR: quantitative real-time polymerase chain reaction; IHC: immunohistochemistry. p values are referred to log-rank test.
Figure 4
Figure 4
Survival analyses according to CD99 mRNA expression z-scores relative to all samples in The Cancer Genome Atlas glioblastoma dataset (PanCancer Atlas). Patients are divided into two groups, with CD99 transcript abundance levels above (CD99 high) or below (CD99 low) the median. Left: overall survival; right: progression-free survival.
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