Lopes-Santos Gabriela, Bernabé Daniel Galera, Miyahara Glauco Issamu, Tjioe Kellen Cristine
Oral Oncology Center, São Paulo State University (Unesp), School of Dentistry, 1193 José Bonifácio St., SP 16015-050, Araçatuba, São Paulo, Brazil.
Oral Oncology Center, São Paulo State University (Unesp), School of Dentistry, 1193 José Bonifácio St., SP 16015-050, Araçatuba, São Paulo, Brazil; Psychoneuroimmunology Laboratory, Psychosomatic Research Center, Oral Oncology Center, São Paulo State University (Unesp), School of Dentistry, 1193 José Bonifácio St, SP 15050-015, Araçatuba, São Paulo, Brazil.
Transl Oncol. 2021 Aug;14(8):101117. doi: 10.1016/j.tranon.2021.101117. Epub 2021 May 13.
Chronic stress leads to the activation of the beta-adrenergic pathway. Its activation has been implicated in the progression of different types of cancer but its role on head and neck squamous cell carcinomas (HNSCCs) remains undefined. The aim of this study was to investigate the influence of the beta-adrenergic pathway activation in the progression of HNSCCs and offer a panel of potential treatments for patients with the active beta-adrenergic pathway. Five hundred and twenty TCGA patients with primary HNSCCs were divided in two groups: ADRB2 / SLC6A2 and ADRB2 / SLC6A2. Differentially expressed genes (DEGs) were identified through differential expression analysis. The association of clinicopathological and genomic features between the groups was analyzed using a bioinformatic approach. Potential drugs for treatment of HNSCC were identified based on the DEGs. There was association between ADRB2 and SLC6A2 expressions with age, race, tumor site, histologic grade, perineural invasion, and HPV p16 status. It was identified 898 DEGs between the groups. High ADRB2/SLC6A2 expression stimulated HNSCC proliferation, adhesion, invasion, and angiogenesis. On the other hand, genes related to cell stemness were downregulated in patients with activation of the beta- adrenergic pathway. Finally, 56 FDA-approved antineoplastic and immunotherapeutic drugs were identified as potential targets for the personalized treatment.
慢性应激导致β-肾上腺素能通路激活。其激活与不同类型癌症的进展有关，但其在头颈部鳞状细胞癌（HNSCC）中的作用仍不明确。本研究旨在探讨β-肾上腺素能通路激活对HNSCC进展的影响，并为β-肾上腺素能通路激活的患者提供一系列潜在治疗方法。520例原发性HNSCC的TCGA患者被分为两组：ADRB2 / SLC6A2组和ADRB2 / SLC6A2组。通过差异表达分析鉴定差异表达基因（DEG）。使用生物信息学方法分析两组之间临床病理和基因组特征的关联。基于DEG确定治疗HNSCC的潜在药物。ADRB2和SLC6A2表达与年龄、种族、肿瘤部位、组织学分级、神经周围侵犯和HPV p16状态之间存在关联。两组之间鉴定出898个DEG。高ADRB2 / SLC6A2表达刺激HNSCC增殖、黏附、侵袭和血管生成。另一方面，在β-肾上腺素能通路激活的患者中，与细胞干性相关的基因下调。最后，56种FDA批准的抗肿瘤和免疫治疗药物被确定为个性化治疗的潜在靶点。
