Glioma Stem Cells: GPRC5A as a Novel Predictive Biomarker and Therapeutic Target Associated with Mesenchymal and Stemness Features

被引:1
作者
Aghamiri, Sara Sadat [1 ]
Amin, Rada [1 ]
机构
[1] Univ Nebraska, Dept Biochem, Lincoln, NE 68503 USA
来源
APPLIED SCIENCES-BASEL | 2024年 / 14卷 / 18期
关键词
glioblastoma; tumor microenvironment; mesenchymal; immune cells; biomarkers; cancer stem cells; EXTRACELLULAR-MATRIX; GLIOBLASTOMA; EXPRESSION; CANCER; RESISTANCE; HYPOXIA; DIFFERENTIATION; PROLIFERATION; MARKERS;
D O I
10.3390/app14188482
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Glioblastoma multiforme (GBM) represents the deadliest form of brain cancer, characterized by complex interactions within its microenvironment. Despite the understanding of GBM biology, GBM remains highly resistant to any therapy. Therefore, defining innovative biomarkers in GBM can provide insights into tumor biology and potential therapeutic targets. In this study, we explored the potential of GPRC5A to serve as a pertinent biomarker for GBM. We utilized the GBM-TCGA dataset and presented the reproducible bioinformatics analysis for our results. We identified that GPRC5A expression was significantly upregulated in GBM compared to normal tissues, with higher levels correlating with poor overall survival (OS) and progression-free interval (PFI). Moreover, it was associated with key genetic mutations, particularly NF1 and PTEN mutations, and strongly correlated with the mesenchymal stem-like phenotype. GPRC5A was also predominantly associated with aggressive GBM features, including hypoxia, high extracellular matrix (ECM) environments, and extensive stromal and immune infiltrations. Its strong correlation with mesenchymal markers and hypoxic regions underscores its potential as a biomarker and therapeutic target in GBM. These findings provide valuable insights into the role of GPRC5A in GBM pathology and its potential impact as a target for GBM stratifications and treatment strategies.
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页数:21
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共 87 条
[61]   'Pseudopalisading' necrosis in glioblastoma: A familiar morphologic feature that links vascular pathology, hypoxia, and angiogenesis [J].
Rong, Yuan ;
Durden, Donald L. ;
Van Meir, Erwin G. ;
Brat, Daniel J. .
JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY, 2006, 65 (06) :529-539
[62]   TISIDB: an integrated repository portal for tumor-immune system interactions [J].
Ru, Beibei ;
Wong, Ching Ngar ;
Tong, Yin ;
Zhong, Jia Yi ;
Zhong, Sophia Shek Wa ;
Wu, Wai Chung ;
Chu, Ka Chi ;
Wong, Choi Yiu ;
Lau, Chit Ying ;
Chen, Ian ;
Chan, Nam Wai ;
Zhang, Jiangwen .
BIOINFORMATICS, 2019, 35 (20) :4200-4202
[63]   Molecular Biomarkers in Glioblastoma: A Systematic Review and Meta-Analysis [J].
Sareen, Heena ;
Ma, Yafeng ;
Becker, Therese M. ;
Roberts, Tara L. ;
de Souza, Paul ;
Powter, Branka .
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2022, 23 (16)
[64]   Tumor microenvironment in glioblastoma: Current and emerging concepts [J].
Sharma, Pratibha ;
Aaroe, Ashley ;
Liang, Jiyong ;
Puduvalli, Vinay K. .
NEURO-ONCOLOGY ADVANCES, 2023, 5 (01)
[65]   The Role of Hypoxia and Cancer Stem Cells in Development of Glioblastoma [J].
Shi, Tingyu ;
Zhu, Jun ;
Zhang, Xiang ;
Mao, Xinggang .
CANCERS, 2023, 15 (09)
[66]   Mesenchymal and Proneural Subtypes of Glioblastoma Disclose Branching Based on GSC Associated Signature [J].
Steponaitis, Giedrius ;
Tamasauskas, Arimantas .
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2021, 22 (09)
[67]   Proliferation of vascular smooth muscle cells in glioblastoma multiforme Laboratory investigation [J].
Takeuchi, Hiroaki ;
Hashimoto, Norichika ;
Kitai, Ryuhei ;
Kubota, Toshihiko ;
Kikuta, Ken-ichiro .
JOURNAL OF NEUROSURGERY, 2010, 113 (02) :218-224
[68]   Targeting Glioblastoma Stem Cells: A Review on Biomarkers, Signal Pathways and Targeted Therapy [J].
Tang, Xuejia ;
Zuo, Chenghai ;
Fang, Pengchao ;
Liu, Guojing ;
Qiu, Yongyi ;
Huang, Yi ;
Tang, Rongrui .
FRONTIERS IN ONCOLOGY, 2021, 11
[69]   GEPIA: a web server for cancer and normal gene expression profiling and interactive analyses [J].
Tang, Zefang ;
Li, Chenwei ;
Kang, Boxi ;
Gao, Ge ;
Li, Cheng ;
Zhang, Zemin .
NUCLEIC ACIDS RESEARCH, 2017, 45 (W1) :W98-W102
[70]   Identification of the retinoic acid-inducible Gprc5a as a new lung tumor suppressor gene [J].
Tao, Qingguo ;
Fujimoto, Junya ;
Men, Taoyan ;
Ye, Xiaofeng ;
Deng, Jiong ;
Lacroix, Ludovic ;
Clifford, John L. ;
Mao, Li ;
Van Pelt, Carolyn S. ;
Lee, J. Jack ;
Lotan, Dafna ;
Lotan, Reuben .
JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE, 2007, 99 (22) :1668-1682