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β2-肾上腺素能受体在口腔鳞状细胞癌中的表达模式及临床意义:一个新兴的预后指标和未来的治疗靶点。

Expression pattern and clinical significance of beta 2-adrenergic receptor in oral squamous cell carcinoma: an emerging prognostic indicator and future therapeutic target.

机构信息

Department of Physiology, King George's Medical University, Lucknow, UP, India.

Speciality of Pathology and Cancer Genetics, Kalyan Singh Super Speciality Cancer Institute, Lucknow, UP, India.

出版信息

Clin Transl Oncol. 2022 Nov;24(11):2191-2199. doi: 10.1007/s12094-022-02879-8. Epub 2022 Aug 2.

Abstract

PURPOSE

Beta 2-Adrenergic Receptor (β2-AR) is significantly overexpressed in various types of malignancies, which is associated with the worst prognosis. However, the role of β2-AR in oral cancer is not well identified. The present study aimed at investigating the β2-AR gene expression and its significance in relation with the clinicopathological features and overall survival of oral squamous cell carcinoma (OSCC) patients.

METHODS

Immunohistochemistry, western blot and quantitative real-time PCR techniques were used to analyze β2-AR protein and mRNA levels in a total of 65 histopathologically confirmed OSCC tissues (case group) and 65 normal tissues (control group) from the oral cavity.

RESULTS

Out of the total of 65 OSCC tissues, 41 tissues (63.1%) exhibited  high expression  for β2-AR protein. Percent positivity and relative density (mean ± SD) of protein were higher in the case group as compared to the control group (positivity 40.31 ± 3.01 vs. 20.46 ± 1.93, p < 0.001; density 2.77 ± 1.17 vs. 1.28 ± 0.37, p < 0.001). In addition, β2-AR mRNA level was also upregulated in patients compared to the controls (2.36 ± 1.30 vs. 1.09 ± 0.42, p < 0.001) and showed a positive correlation with immunostaining of protein in OSCC (r = 0.48, p = 0.011). High β2-AR protein expression was significantly associated with multiple risk habits (p = 0.045), histological differentiation (p = 0.013), clinical TNM stages (p = 0.014), and poor survival (p = 0.006) of patients. In the Cox proportional hazards model, β2-AR was identified as a prognostic biomarker of OSCC (p = 0.047).

CONCLUSION

β2-AR protein level is identified as an independent significant prognostic factor in patients with oral carcinoma.

摘要

目的

β2-肾上腺素能受体(β2-AR)在各种类型的恶性肿瘤中显著过表达,与预后最差相关。然而,β2-AR 在口腔癌中的作用尚未明确。本研究旨在探讨β2-AR 基因表达及其与口腔鳞状细胞癌(OSCC)患者临床病理特征和总生存的关系。

方法

采用免疫组织化学、Western blot 和实时定量 PCR 技术分析了 65 例经组织病理学证实的口腔 OSCC 组织(病例组)和 65 例口腔正常组织(对照组)中β2-AR 蛋白和 mRNA 水平。

结果

在 65 例 OSCC 组织中,有 41 例(63.1%)β2-AR 蛋白表达高。病例组的阳性率和相对密度(平均值±标准差)均高于对照组(阳性率 40.31±3.01%对 20.46±1.93%,p<0.001;密度 2.77±1.17 对 1.28±0.37,p<0.001)。此外,与对照组相比,患者的β2-AR mRNA 水平也升高(2.36±1.30 对 1.09±0.42,p<0.001),并与 OSCC 中蛋白免疫染色呈正相关(r=0.48,p=0.011)。高β2-AR 蛋白表达与多种危险因素(p=0.045)、组织学分化(p=0.013)、临床 TNM 分期(p=0.014)和不良预后(p=0.006)显著相关。在 Cox 比例风险模型中,β2-AR 被确定为 OSCC 的预后生物标志物(p=0.047)。

结论

β2-AR 蛋白水平被确定为口腔癌患者独立的显著预后因素。

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