Anti-Apoptotic and Anti-Oxidant Proteins in Glioblastomas: Immunohistochemical Expression of Beclin and DJ-1 and Its Correlation with Prognosis
by
Elia Guadagno 1,*, Giorgio Borrelli 1, Sara Pignatiello 1, Annalidia Donato 2, Ivan Presta 3
, Biagio Arcidiacono 3, Natalia Malara 4, Domenico Solari 5, Teresa Somma 5, Paolo Cappabianca 5, Giuseppe Donato 3 and Marialaura Del Basso De Caro 1
Elia Guadagno 1,*, Giorgio Borrelli 1, Sara Pignatiello 1, Annalidia Donato 2, Ivan Presta 3, Biagio Arcidiacono 3, Natalia Malara 4, Domenico Solari 5, Teresa Somma 5, Paolo Cappabianca 5, Giuseppe Donato 3 and Marialaura Del Basso De Caro 1
1
Department of Advanced Biomedical Sciences, Pathology Section, Federico II University of Naples, 80131 Napoli, Italy
2
Department of Medical and Surgical Sciences–University of Catanzaro “Magna Graecia”–viale Europa, 88100 Catanzaro, Italy
3
Department of Health Sciences, University of Catanzaro “Magna Græcia”-viale Europa, 88100 Catanzaro, Italy
4
Department of Clinical and Experimental Medicine–University of Catanzaro “Magna Graecia”–viale Europa, 88100 Catanzaro, Italy
5
Department of Neurosciences and Reproductive and Odontostomatological Sciences, Division of Neurosurgery, Federico II University of Naples, 80131 Napoli, Italy
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(16), 4066; https://doi.org/10.3390/ijms20164066
Received: 13 July 2019 / Revised: 13 August 2019 / Accepted: 14 August 2019 / Published: 20 August 2019
(This article belongs to the Special Issue Apoptosis and Autophagy: The Double Edge in Cancer Development and Progression and in Other Human Diseases 2.0)
DJ-1 deglycase is a protein with anti-oxidative and anti-apoptotic properties and its role in oncogenesis is controversial. Indeed in primary breast cancer and non-small-cell lung carcinoma, its higher expression was shown in more aggressive tumors while in other neoplasms (e.g., pancreatic adenocarcinoma), higher expression was related to better prognosis. Beclin has a relevant role in autophagy and cellular death regulation, processes that are well known to be impaired in neoplastic cells. DJ-1 shows the ability to modulate signal transduction. It can modulate autophagy through many signaling pathways, a process that can mediate either cell survival or cell death depending on the circumstances. Previously, it has been suggested that the involvement of DJ-1 in autophagy regulation may play a role in tumorigenesis. The aim of our study was to investigate the link between DJ-1 and Beclin-1 in glioblastoma through the immunohistochemical expression of such proteins and to correlate the data obtained with prognosis. Protein expression was assessed by immunohistochemistry and the immunoscores were correlated with clinicopathologic parameters. Kaplan–Meier survival curves were generated. A statistically significant association between DJ-1 score and recurrence (p = 0.0189) and between the former and Isocitrate Dehydrogenase 1 (IDH1) mutation (p = 0.0072) was observed. Kaplan–Meier survival curve analysis revealed that a higher DJ-1 score was associated with longer overall survival (p = 0.0253, ĸ2 = 5.005). Furthermore, an unexpected direct correlation (p = 0.0424, r = 0.4009) between DJ-1 and Beclin score was evident. The most significant result of the present study was the evidence of high DJ-1 expression in IDH-mutant tumors and in cases with longer overall survival. This finding could aid, together with IDH1, in the identification of glioblastomas with better prognosis.
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Keywords:
cell apoptosis; autophagy; glioblastoma; IDH1
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MDPI and ACS Style
Guadagno, E.; Borrelli, G.; Pignatiello, S.; Donato, A.; Presta, I.; Arcidiacono, B.; Malara, N.; Solari, D.; Somma, T.; Cappabianca, P.; Donato, G.; Del Basso De Caro, M. Anti-Apoptotic and Anti-Oxidant Proteins in Glioblastomas: Immunohistochemical Expression of Beclin and DJ-1 and Its Correlation with Prognosis. Int. J. Mol. Sci. 2019, 20, 4066.
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