Research Paper Volume 13, Issue 6 pp 9085—9107

Nidogen-1 expression is associated with overall survival and temozolomide sensitivity in low-grade glioma patients

Baiwei Zhang1, *, , Cheng Xu2,3, *, , Junfeng Liu1, , Jinsheng Yang4, , Qinglei Gao2,3, , Fei Ye1, ,

  • 1 Department of Neurosurgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
  • 2 Cancer Biology Research Center, Key Laboratory of the Ministry of Education, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
  • 3 Department of Gynecology and Obstetrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
  • 4 Department of Neurosurgery, The First Affiliated Hospital of Henan University of Science and Technology, Luoyang, China
* Equal contribution

Received: August 8, 2020       Accepted: February 16, 2021       Published: March 18, 2021      

https://doi.org/10.18632/aging.202789
How to Cite

Copyright: © 2021 Zhang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

We investigated the prognostic significance of nidogen-1 (NID1) in glioma. Oncomine, GEPIA, UALCAN, CCGA database analyses showed that NID1 transcript levels were significantly upregulated in multiple cancer types, including gliomas. Quantitative RT-PCR analyses confirmed that NID1 expression was significantly upregulated in glioma tissues compared to paired adjacent normal brain tissue samples (n=9). NID1 silencing enhanced in vitro apoptosis and the temozolomide sensitivity of U251 and U87-MG glioma cells. Protein-protein interaction network analysis using the STRING and GeneMANIA databases showed that NID1 interacts with several extracellular matrix proteins. TIMER database analysis showed that NID1 expression in low-grade gliomas was associated with tumor infiltration of B cells, CD4+ and CD8+ T cells, macrophages, neutrophils, and dendritic cells. Kaplan-Meier survival curve analysis showed that low-grade gliomas patients with high NID1 expression were associated with shorter overall survival. However, NID1 expression was not associated with overall survival in glioblastoma multiforme patients. These findings demonstrate that NID1 expression in glioma tissues is associated with overall survival of low-grade glioma patients and temozolomide sensitivity. NID1 is thus a potential prognostic biomarker and therapeutic target in low-grade glioma patients.

Abbreviations

NID1: Nidogen-1; TMZ: Temozolomide; DEGs: Differently expressed genes; CNS: Central nervous system; EMT: Epithelial-mesenchymal transition; ECM: The extracellular matrix; NSCLC: Non-small cell lung cancer; HCC: Hepatocellular carcinoma; GEPIA: Gene Expression Profiling Interactive Analysis; CGGA: Chinese Glioma Genome Atlas; HPA: Human Protein Atlas; OS: Overall survival; WHO: World Health Organization; LGG: low-grade glioma; GBM: Glioblastoma multiforme; siRNA: small interfering RNA; TPM: Transcripts Per Million; GO: gene ontology; KEGG: Kyoto encyclopedia of genes and genomes; PPI: Protein-protein interaction; The Cancer Genome Atlas: TCGA; HR: Hazard ratio; BMS/BM: Basement membranes/ basement membrane; ADDWOC: Autosomal dominant Dandy-Walker malformation and occipital cephaloceles; BBB: Blood-brain barrier.