2. Academic Validation
  3. Pan-cancer analysis of the role of α2C-adrenergic receptor (ADRA2C) in human tumors and validation in glioblastoma multiforme models

Pan-cancer analysis of the role of α2C-adrenergic receptor (ADRA2C) in human tumors and validation in glioblastoma multiforme models

  • J Cancer. 2024 Sep 9;15(17):5691-5709. doi: 10.7150/jca.98240.
Xiaoxiao Zhang 1,  Huitong Chen 1,  Chenyang Wang 2,  Chan Chen 1,  Liyan Liu 1,  Shuangfa Nie 2,  Xiang Gao 3,  Ning Huang 1,  Junli Chen 1 4
Affiliations

Affiliations

  • 1 Department of Pathophysiology, West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu 610041, China.
  • 2 Department of Gastrointestinal Surgery, the First Affiliated Hospital of Hebei North University, Zhangjiakou 075061, China.
  • 3 Department of Neurosurgery and Institute of Neurosurgery, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University and Collaborative Innovation Center for Biotherapy, Chengdu 610041, China.
  • 4 NHC Key Laboratory of Chronobiology (Sichuan University), Chengdu 610041, China.
PMID: 39308687 DOI: 10.7150/jca.98240
Abstract

Background: Several studies have reported the relationship between α2C-adrenergic receptor (ADRA2C) and both neoplastic and non-neoplastic diseases. However, a comprehensive pan-cancer analysis is currently lacking. Methods: Utilizing the RNA Sequencing (RNA-seq) datasets from The Cancer Genome Atlas (TCGA) database, the roles of ADRA2C in human pan-cancer were analyzed through a variety of bioinformatics approaches, including R programming language and single-cell Sequencing data analysis, et al. Besides, cell migration assay and immunochemistry were employed to further validate the role of ADRA2C in glioblastoma multiforme (GBM) cell lines and GBM mouse model. Results: A total of 33 Cancer types were involved in this study. It was revealed that the expression level of ADRA2C varied across different clinical stages in patients with breast invasive carcinoma (BRCA), esophageal adenocarcinoma (ESCA), kidney renal papillary cell carcinoma (KIRP) and lung squamous cell carcinoma (LUSC). Meanwhile, it was found that ADRA2C may play roles in prognosis of adrenocortical carcinoma (ACC), glioblastoma multiforme and lower grade glioma (GBM-LGG), and uveal melanoma (UVM). Functional enrichment analysis suggested that ADRA2C expression level was highly correlated with neuronal system-related pathways. Moreover, ADRA2C may be a promising diagnostic marker for cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC), cholangiocarcinoma (CHOL), GBM, GBMLGG, kidney chromophobe (KICH), and KIRP. Additionally, ADRA2C expression level was correlated with the levels of several infiltrating cells and immune checkpoint genes. Besides, the single-cell Sequencing data analysis indicated that ADRA2C played a role in multiple tumor development processes in GBM, retinoblastoma (RB), and UVM. Finally, in vitro and in vivo experiments confirmed that the expression level of ADRA2C may be associated with glioma cell migration, Apoptosis, and invasion. Conclusion: ADRA2C exhibited to play a notable role in several Cancer types, suggesting that ADRA2C could serve as a promising biomarker or target for Cancer diagnosis, prognosis, and treatment, particularly for GBM.

Keywords

apoptosis; glioblastoma multiforme; invasion; pan-cancer analysis; prognosis; α2C-adrenergic receptor.

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