Zhang Xiaoxiao, Chen Huitong, Wang Chenyang, Chen Chan, Liu Liyan, Nie Shuangfa, Gao Xiang, Huang Ning, Chen Junli
Department of Pathophysiology, West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu 610041, China.
Department of Gastrointestinal Surgery, the First Affiliated Hospital of Hebei North University, Zhangjiakou 075061, China.
J Cancer. 2024 Sep 9;15(17):5691-5709. doi: 10.7150/jca.98240. eCollection 2024.
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. 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, . 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. 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, and experiments confirmed that the expression level of ADRA2C may be associated with glioma cell migration, apoptosis, and invasion. 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.
多项研究报道了α2C-肾上腺素能受体（ADRA2C）与肿瘤性和非肿瘤性疾病之间的关系。然而，目前缺乏全面的泛癌分析。利用来自癌症基因组图谱（TCGA）数据库的RNA测序（RNA-seq）数据集，通过多种生物信息学方法，包括R编程语言和单细胞测序数据分析，分析了ADRA2C在人类泛癌中的作用。此外，采用细胞迁移试验和免疫化学方法进一步验证ADRA2C在多形性胶质母细胞瘤（GBM）细胞系和GBM小鼠模型中的作用。本研究共涉及33种癌症类型。结果显示，在乳腺浸润性癌（BRCA）、食管腺癌（ESCA）、肾肾乳头状细胞癌（KIRP）和肺鳞状细胞癌（LUSC）患者中，ADRA2C的表达水平在不同临床阶段有所不同。同时，发现ADRA2C可能在肾上腺皮质癌（ACC）、多形性胶质母细胞瘤和低级别胶质瘤（GBM-LGG）以及葡萄膜黑色素瘤（UVM）的预后中发挥作用。功能富集分析表明，ADRA2C表达水平与神经系统相关通路高度相关。此外，ADRA2C可能是宫颈鳞状细胞癌和宫颈管腺癌（CESC）、胆管癌（CHOL）、GBM、GBM-LGG、肾嫌色细胞癌（KICH）和KIRP的一个有前景的诊断标志物。此外，ADRA2C表达水平与几种浸润细胞和免疫检查点基因的水平相关。此外，单细胞测序数据分析表明，ADRA2C在GBM、视网膜母细胞瘤（RB）和UVM的多个肿瘤发生过程中发挥作用。最后，实验证实ADRA2C的表达水平可能与胶质瘤细胞的迁移、凋亡和侵袭有关。ADRA2C在几种癌症类型中表现出显著作用，表明ADRA2C可作为一种有前景的生物标志物或癌症诊断、预后和治疗的靶点，特别是对于GBM。
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