PMID- 37587203
OWN - NLM
STAT- MEDLINE
DCOM- 20230818
LR  - 20231123
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 13
IP  - 1
DP  - 2023 Aug 16
TI  - Tetraspanins predict the prognosis and characterize the tumor immune 
      microenvironment of glioblastoma.
PG  - 13317
LID - 10.1038/s41598-023-40425-w [doi]
LID - 13317
AB  - Glioblastoma (GBM) is the most aggressive and lethal primary brain tumor. 
      Conventional treatments have not achieved breakthroughs in improving survival. 
      Therefore, novel molecular targets and biomarkers need to be identified. As 
      signal transduction docks on the cell membrane, tetraspanins (TSPANs) are 
      associated with various tumors; however, research on their role in GBM remains 
      extremely scarce. Gene expression and clinicopathological characteristic data 
      were obtained from GEPIA, CGGA, HPA, cBioPortal, and GSCA databases to analyze 
      the mRNA and protein expression levels, prognostic value, clinical relevance, 
      mutation status, and targeted drug sensitivity of TSPANs in GBM. Gene set 
      enrichment analysis (GSEA), Gene Ontology (GO), and the Kyoto Encyclopedia of 
      Genes and Genomes (KEGG) analysis were used for biological process enrichment. 
      Data from TCGA and TCIA were used to construct the tumor immune microenvironment 
      landscape of TSPANs. Different R software algorithms were used to analyze the 
      immune score, immune cell infiltration, and immune checkpoint correlation. 
      Univariate and multivariate analyses were performed for TSPAN4, which had the 
      most significant predictive prognostic value, and a nomogram model was 
      constructed to predict individual outcomes. The expression and function of TSPAN4 
      were verified in vitro. TSPAN3/4/6/11/12/18/23/24/25/26/27/28/29/30/31expressions 
      were significantly upregulated in GBM, and TSPAN3/4/6/11/18/24/25/26/29/30 were 
      strongly correlated with prognosis. The expression of multiple TSPANs 
      significantly correlated with 1p/19q co-deletion status, IDH mutation status, 
      recurrence, age, and tumor grade. GSEA and GO analyses revealed the potential 
      contribution of TSPANs in cell adhesion and migration. Immune correlation 
      analysis revealed that TSPANs are related to the formation of the GBM tumor 
      microenvironment (TME) and may influence immunotherapy outcomes. TSPAN4 is an 
      independent prognostic factor and TSPAN4 knockdown has been demonstrated to 
      strongly inhibit glioma cell proliferation, invasion, and migration in vitro. We 
      comprehensively elaborated the prognostic value and potential role of 
      differentially expressed TSPANs in GBM, including molecules that scientists have 
      previously overlooked. This study provides a novel and comprehensive perspective 
      on the pathological mechanisms of GBM and the future direction of individualized 
      tumor immunotherapy, which may be a critical link between GBM malignant 
      progression and TME remodeling.
CI  - (c) 2023. Springer Nature Limited.
FAU - Li, Yu-Chao
AU  - Li YC
AD  - Department of Nuclear Medicine, The First Affiliated Hospital of Naval Medical 
      University, Shanghai, China.
FAU - Wu, Yue
AU  - Wu Y
AD  - Department of Neurosurgery & Brain and Nerve Research Laboratory, The First 
      Affiliated Hospital of Soochow University, Suzhou, China.
FAU - Chen, Gang
AU  - Chen G
AD  - Department of Neurosurgery & Brain and Nerve Research Laboratory, The First 
      Affiliated Hospital of Soochow University, Suzhou, China.
FAU - Zhu, Li-Zhi
AU  - Zhu LZ
AD  - Department of Nuclear Medicine, The First Affiliated Hospital of Naval Medical 
      University, Shanghai, China.
FAU - Luo, Xiu
AU  - Luo X
AD  - Department of Nuclear Medicine, The First Affiliated Hospital of Naval Medical 
      University, Shanghai, China.
FAU - Nie, Qian-Qian
AU  - Nie QQ
AD  - Department of Neurology & Brain and Nerve Research Laboratory, The First 
      Affiliated Hospital of Soochow University, Suzhou, China. nqq9791@163.com.
FAU - Zhang, Lu
AU  - Zhang L
AD  - Department of Nuclear Medicine, The First Affiliated Hospital of Naval Medical 
      University, Shanghai, China. courageunder@hotmail.com.
FAU - Zuo, Chang-Jing
AU  - Zuo CJ
AD  - Department of Nuclear Medicine, The First Affiliated Hospital of Naval Medical 
      University, Shanghai, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20230816
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
SB  - IM
MH  - Humans
MH  - *Glioblastoma/genetics
MH  - Tumor Microenvironment/genetics
MH  - Prognosis
MH  - *Glioma
MH  - Nomograms
PMC - PMC10432458
COIS- The authors declare no competing interests.
EDAT- 2023/08/17 00:42
MHDA- 2023/08/18 06:42
PMCR- 2023/08/16
CRDT- 2023/08/16 23:23
PHST- 2023/02/14 00:00 [received]
PHST- 2023/08/10 00:00 [accepted]
PHST- 2023/08/18 06:42 [medline]
PHST- 2023/08/17 00:42 [pubmed]
PHST- 2023/08/16 23:23 [entrez]
PHST- 2023/08/16 00:00 [pmc-release]
AID - 10.1038/s41598-023-40425-w [pii]
AID - 40425 [pii]
AID - 10.1038/s41598-023-40425-w [doi]
PST - epublish
SO  - Sci Rep. 2023 Aug 16;13(1):13317. doi: 10.1038/s41598-023-40425-w.