TY - JOUR
T1 - Prognostic Neurotransmitter Receptors Genes Are Associated with Immune Response, Inflammation and Cancer Hallmarks in Brain Tumors
AU - Belotti, Yuri
AU - Tolomeo, Serenella
AU - Yu, Rongjun
AU - Lim, Wan Teck
AU - Lim, Chwee Teck
N1 - Funding Information:
Funding: This work was conceived and carried out at the Institute for Health Innovation & Technology (iHealthtech), National University of Singapore. Y.B. was supported by iHealthtech (Grant No. R-722-007-004-731), National University of Singapore. S.T. was supported by the Singapore Ministry of Education Grant (Grant No. MOE2017-SSRTG-026). R.Y. was supported by the Singapore Ministry of Education Grant (Grant No. MOE2017-SSRTG-026). W.-T.L. was supported by the National Medical Research Council (Grant No. NMRC/CSA-INV/0025/2017). C.T.L. was supported by the Institute for Health Innovation and Technology (iHealthtech), National University of Singapore (Grant No. R-722-007-004-731) and Mechanobiology Institute (MBI) Seed Grant (Grant No. R-714-106-002-135), National University of Singapore.
Publisher Copyright:
© 2022 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2022/5/21
Y1 - 2022/5/21
N2 - Glioblastoma multiforme (GBM) is one of the most aggressive forms of cancer. Neurotransmitters (NTs) have recently been linked with the uncontrolled proliferation of cancer cells, but the role of NTs in the progression of human gliomas is still largely unexplored. Here, we investigate the genes encoding for neurotransmitter receptors (NTRs) by analyzing public transcriptomic data from GBM and LGG (low-grade glioma) samples. Our results showed that 50 out of the 98 tested NTR genes were dysregulated in brain cancer tissue. Next, we identified and validated NTR-associated prognostic gene signatures for both LGG and GBM. A subset of 10 NTR genes (DRD1, HTR1E, HTR3B, GABRA1, GABRA4, GABRB2, GABRG2, GRIN1, GRM7, and ADRA1B) predicted a positive prognosis in LGG and a negative prognosis in GBM. These genes were progressively downregulated across glioma grades and exhibited a strong negative correlation with genes associated with immune response, inflammasomes, and established cancer hallmarks genes in lower grade gliomas, suggesting a putative role in inhibiting cancer progression. This study might have implications for the development of novel therapeutics and preventive strategies that target regulatory networks associated with the link between the autonomic nervous system, cancer cells, and the tumor microenvironment.
AB - Glioblastoma multiforme (GBM) is one of the most aggressive forms of cancer. Neurotransmitters (NTs) have recently been linked with the uncontrolled proliferation of cancer cells, but the role of NTs in the progression of human gliomas is still largely unexplored. Here, we investigate the genes encoding for neurotransmitter receptors (NTRs) by analyzing public transcriptomic data from GBM and LGG (low-grade glioma) samples. Our results showed that 50 out of the 98 tested NTR genes were dysregulated in brain cancer tissue. Next, we identified and validated NTR-associated prognostic gene signatures for both LGG and GBM. A subset of 10 NTR genes (DRD1, HTR1E, HTR3B, GABRA1, GABRA4, GABRB2, GABRG2, GRIN1, GRM7, and ADRA1B) predicted a positive prognosis in LGG and a negative prognosis in GBM. These genes were progressively downregulated across glioma grades and exhibited a strong negative correlation with genes associated with immune response, inflammasomes, and established cancer hallmarks genes in lower grade gliomas, suggesting a putative role in inhibiting cancer progression. This study might have implications for the development of novel therapeutics and preventive strategies that target regulatory networks associated with the link between the autonomic nervous system, cancer cells, and the tumor microenvironment.
KW - bioinformatics
KW - brain tumors
KW - glioblastoma
KW - precision medicine
KW - prognostic biomarker
KW - TCGA
KW - transcriptomics
UR - http://www.scopus.com/inward/record.url?scp=85130501860&partnerID=8YFLogxK
U2 - 10.3390/cancers14102544
DO - 10.3390/cancers14102544
M3 - Journal article
SN - 2072-6694
VL - 14
JO - Cancers
JF - Cancers
IS - 10
M1 - 2544
ER -
