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

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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.

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Acknowledgements

We would like to express our gratitude to all the patients and volunteers who participated in this study. The authors are also grateful to all the clinicians and researchers who helped in patient recruitment and technical assistance. Dr. Sachil Kumar (NAUSS, Riyadh, Saudi Arabia) was also extremely helpful in standardizing the biomarker in western blotting.

Funding

Present work was financially supported by the Council of Science and Technology, Uttar Pradesh (U.P.C.S.T), Lucknow, India (letter no. CST/SERPD/D‑212, dated 11.05.2015).

Author information

Author notes

  1. Akhilesh Krishna

    Present address: Speciality of Pathology and Cancer Genetics, Kalyan Singh Super Speciality Cancer Institute, Lucknow, UP, India

  2. Sujit Kumar Mohanty

    Present address: Indiana Centre for Regenerative Medicine and Engineering, Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, USA

Authors and Affiliations

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

    Akhilesh Krishna, Vineeta Singh & Shraddha Singh

  2. Department of Biotechnology, Babasaheb Bhimrao Ambedkar University, Lucknow, UP, India

    Vineeta Singh

  3. Department of Microbiology, King George’s Medical University, Lucknow, UP, India

    Nishtha Singh

  4. Division of Endocrinology, CSIR-Central Drug Research Institute, Lucknow, UP, India

    Sujit Kumar Mohanty & Rajender Singh

  5. Department of Surgical Oncology, King George’s Medical University, Lucknow, UP, India

    Vijay Kumar

  6. Department of Pathology, King George’s Medical University, Lucknow, UP, India

    Uma Shankar Singh

  7. Department of Oral and Maxillofacial Surgery, King George’s Medical University, Lucknow, UP, India

    Rakesh Kumar Singh

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Contributions

AK, SS contributed to the study conception and design. Material preparation, data collection and analysis were performed by AK, VS, RS and SKM. Clinical and Pathological assistance provided by VK, RKS, USS and NS. The first draft of the manuscript was written by AK and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Akhilesh Krishna or Shraddha Singh.

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No conflict of interest/competing interests to declare.

Ethical approval

This study was approved by the Institutional Ethics Committee of King George’s Medical University, Lucknow, U.P, India (letter no. 494/R.Cell-15 Dated 24/02/2015).

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All included patients got approved information materials and have provided written consent.

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Krishna, A., Singh, V., Singh, N. et al. Expression pattern and clinical significance of beta 2-adrenergic receptor in oral squamous cell carcinoma: an emerging prognostic indicator and future therapeutic target. Clin Transl Oncol 24, 2191–2199 (2022). https://doi.org/10.1007/s12094-022-02879-8

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