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Differential Expression of SRY-Related HMG-Box Transcription Factor 2, Oligodendrocyte Lineage Transcription Factor 2, and Zinc Finger E-Box Binding Homeobox 1 in Serum-Derived Extracellular Vesicles: Implications for Mithramycin Sensitivity and Targeted Therapy in High-Grade Glioma.
Patnam, Sreekanth; Majumder, Biswanath; Joshi, Parth; Singh, Anula Divyash; Nagalla, Balakrishna; Kumar, Dilli; Biswas, Manjusha; Ranjan, Alok; Majumder, Pradip K; Rengan, Aravind Kumar; Kamath, Ajith V; Ray, Amitava; Manda, Sasidhar Venkata.
Afiliación
  • Patnam S; Apollo Hospitals Educational and Research Foundation (AHERF), Hyderabad, Hyderabad, Telangana 500033, India.
  • Majumder B; Department of Biomedical Engineering, Indian Institute of Technology, Kandi, Hyderabad 502285, India.
  • Joshi P; Farcast Biosciences, Bangalore, Karnataka 560100, India.
  • Singh AD; Oncology Division, Bugworks Research India Pvt. Ltd., C-CAMP, Bangalore, Karnataka 560065, India.
  • Nagalla B; Department of Neurosurgery, Apollo Hospitals, Hyderabad, Telangana 500029, India.
  • Kumar D; Apollo Hospitals Educational and Research Foundation (AHERF), Hyderabad, Hyderabad, Telangana 500033, India.
  • Biswas M; Department of Biomedical Engineering, Indian Institute of Technology, Kandi, Hyderabad 502285, India.
  • Ranjan A; Apollo Institute of Medical Sciences and Research, Hyderabad, Telangana, Hyderabad 500090, India.
  • Majumder PK; Farcast Biosciences, Bangalore, Karnataka 560100, India.
  • Rengan AK; Farcast Biosciences, Bangalore, Karnataka 560100, India.
  • Kamath AV; Department of Neurosurgery, Apollo Hospitals, Hyderabad, Telangana 500029, India.
  • Ray A; Department of Cancer Biology, Praesidia Biotherapeutics, 1167 Massachusetts Avenue, Arlington, Massachusetts 02476, United States.
  • Manda SV; Department of Biomedical Engineering, Indian Institute of Technology, Kandi, Hyderabad 502285, India.
ACS Pharmacol Transl Sci ; 7(1): 137-149, 2024 Jan 12.
Article en En | MEDLINE | ID: mdl-38230292
ABSTRACT
Glioblastoma multiforme (GBM) is the most aggressive type of glioma and is often resistant to traditional therapies. Evidence suggests that glioma stem cells (GSCs) contribute to this resistance. Mithramycin (Mit-A) targets GSCs and exhibits antitumor activity in GBM by affecting transcriptional targets such as SRY-related HMG-box transcription factor 2 (SOX2), oligodendrocyte lineage transcription factor 2 (OLIG2), and zinc finger E-box binding homeobox 1 (ZEB1). However, its clinical use has been limited by toxicity. This study explored the diagnostic potential of serum extracellular vesicles (EVs) to identify Mit-A responders. Serum EVs were isolated from 70 glioma patients, and targeted gene expression was analyzed using qRT-PCR. Using chemosensitivity assay, we identified 8 Mit-A responders and 17 nonresponders among 25 glioma patients. The M-score showed a significant correlation (p = 0.045) with isocitrate dehydrogenase 1 mutation but not other clinical variables. The genes SOX2 (p = 0.005), OLIG2 (p = 0.003), and ZEB1 (p = 0.0281) were found to be upregulated in the responder EVs. SOX2 had the highest diagnostic potential (AUC = 0.875), followed by OLIG2 (AUC = 0.772) and ZEB1 (AUC = 0.632).The combined gene panel showed significant diagnostic efficacy (AUC = 0.956) through logistic regression analysis. The gene panel was further validated in the serum EVs of 45 glioma patients. These findings highlight the potential of Mit-A as a targeted therapy for high-grade glioma based on differential gene expression in serum EVs. The gene panel could serve as a diagnostic tool to predict Mit-A sensitivity, offering a promising approach for personalized treatment strategies and emphasizing the role of GSCs in therapeutic resistance.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Tipo de estudio: Diagnostic_studies / Prognostic_studies Idioma: En Revista: ACS Pharmacol Transl Sci Año: 2024 Tipo del documento: Article País de afiliación: India Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Tipo de estudio: Diagnostic_studies / Prognostic_studies Idioma: En Revista: ACS Pharmacol Transl Sci Año: 2024 Tipo del documento: Article País de afiliación: India Pais de publicación: Estados Unidos