J Cancer 2021; 12(17):5193-5205. doi:10.7150/jca.59948 This issue
1. Medical Research Center, Fujian Maternity and Child Health Hospital, Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, China.
2. Key Laboratory of Technical Evaluation of Fertility Regulation for Non-human Primate, National Health and Family Planning Commission, Fuzhou, Fujian, China.
3. Department of neurosurgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
4. State Key Laboratory for Medical Genomics, Shanghai Institute of Hematology, Rui-Jin Hospital Affiliated to School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
*These authors equally contributed to this work.
Background: Analysis of the differentially expressed genes between lower grade glioma (LGG) and glioblastoma (GBM) will identify genes involved in a more aggressive phenotype of glioma.
Methods: Differentially expressed genes between GBM and LGG were identified using published datasets. Kaplan-Meier estimator was used to determine the overall survival of different groups of glioma patients. The biological functions of CDHR1 in glioma were tested using CCK-8 and trans-well assays.
Results: CCDC109B, CD58, CLIC1, EFEMP2, EMP3, LAMC1, LGALS1, PDLIM1 and TNFRSF1A were over-expressed, while, CDHR1 was down-regulated in GBM in The Cancer Genome Atlas (TCGA), Chinese Glioma Genome Atlas (CGGA), GSE4412 and GSE43378 datasets. Compared with normal brain tissues, CDHR1 was down-regulated in glioma tissues. And low expression of CDHR1 was an unfavorable prognostic factor in glioma. Moreover, CDHR1 was lowly expressed in mesenchymal GBM subtype and lower expression of CDHR1 was associated with the worse clinical prognosis of GBM. Furthermore, CDHR1 was down-regulated in astrocytoma LGG subtype and low expression of CDHR1 was a bad prognosis of LGG. CDHR1 expression levels were also associated with IDH mutation. IDH mutant LGG or GBM patients were with higher CDHR1 expression. High expression of CDHR1 was a favorable prognosis in IDH mutant or IDH wild type LGG patients. CHDR1 expression was associated with MGMT methylation and CDHR1 was down-regulated in chemotherapy un-responsive LGG patients. CDHR1 was an independent prognostic factor and negatively associated with EMP3 expression. Glioma patients with low CDHR1 and high EMP3 expression had worse clinical outcomes. At last, we showed that over-expression of CDHR1 could inhibit glioma cell growth and invasion.
Conclusion: Low expression of CDHR1 was an independent unfavorable prognostic factor in glioma.
Keywords: CDHR1, Lower grade glioma, Glioblastoma, TCGA, GEO datasets