Investigating the Relationship Between Serum Amphiregulin Levels and Natural Killer Cell Activity in Patients with Non-Small Cell Lung Cancer and Healthy Individuals

Authors

DOI:

https://doi.org/10.58600/eurjther2848

Keywords:

Amphiregulin (AREG), Natural Killer (NK) Cells, Non-Small Cell Lung Cancer (NSCLC), immune regulation

Abstract

Objective: Amphiregulin (AREG), which is known as a ligand for the epidermal growth factor receptor (EGFR), is widely expressed by cancerous and immune cells. By activating EGFR signaling, AREG enhances GLUT1 expression. It also promotes intracellular glucose uptake. In this way it supports glycolysis and lactate production. This metabolic hallmark is known as the Warburg effect. A similar glycolytic shift occurs in activated natural killer (NK) cells, which are essential components of antiviral and antitumor immunity. The aim of this study is to investigate the relationship between serum AREG levels and NK cell activation in patients with non-small cell lung cancer (NSCLC).

Methods: This is a case-control study which includes 40 NSCLC patients and 40 healthy controls. Serum AREG levels were measured by ELISA and NK cell activation was assessed by using flow cytometric analysis of CD107a, CD69, CD314 (NKG2D), and CD337 (NKp30) parameters.

Results: Serum AREG levels were significantly lower in NSCLC patients compared to healthy individuals. Although the overall percentage of NK cells was increased in patients, expression of activation markers especially CD107a was reduced. Correlation analysis revealed weak negative associations between AREG levels and expression of CD107a, CD69, CD314, and CD337.

Conclusion: Collectively, these findings suggest that reduced serum AREG levels may be linked to impaired NK cell activation in NSCLC, potentially through limited glucose uptake, highlighting AREG as a potential regulator of immune metabolism and a candidate for further investigation in tumor immune evasion.

Author Biographies

Rumeysa Duyuran, Respiratory Diseases and Respiratory Surgery Research and Practice Center, Gaziantep University, Gaziantep, Türkiye

PhD, 

Demet Taşdemir, Respiratory Diseases and Respiratory Surgery Research and Practice Center, Gaziantep University, Gaziantep, Türkiye

PhD, 

Pınar Yumrutaş, Respiratory Diseases and Respiratory Surgery Research and Practice Center, Gaziantep University, Gaziantep, Türkiye

PhD

Hülya Güven, Respiratory Diseases and Respiratory Surgery Research and Practice Center, Gaziantep University, Gaziantep, Türkiye

PhD

Nurevşan Kuşdoğan, Respiratory Diseases and Respiratory Surgery Research and Practice Center, Gaziantep University, Gaziantep, Türkiye

MD, PhD, Department of Thoracic Surgery, Faculty of Medicine, Gaziantep City Hospital, Gaziantep, Türkiye

Zeynep Sav Tunca, Respiratory Diseases and Respiratory Surgery Research and Practice Center, Gaziantep University, Gaziantep, Türkiye

MD, PhD, Department of Physiology, Faculty of Medicine, Gaziantep University, Gaziantep, Türkiye

Serdar Öztuzcu, Respiratory Diseases and Respiratory Surgery Research and Practice Center, Gaziantep University, Gaziantep, Türkiye

PhD, Department of Medical Biology, Faculty of Medicine, Gaziantep University, Gaziantep, Türkiye

Esra Bozgeyik, Department of Medical Biology, Faculty of Medicine, Adıyaman University, Adıyaman, Türkiye

PhD

Ahmet Ferudun Işık, Respiratory Diseases and Respiratory Surgery Research and Practice Center, Gaziantep University, Gaziantep, Türkiye

MD, Department of Thoracic Surgery, Faculty of Medicine, Gaziantep University, Gaziantep, Türkiye

Ahmet Ulusan, Department of Thoracic Surgery, Faculty of Medicine, Gaziantep University, Gaziantep, Türkiye

MD

Hülya Çiçek, Department of Medical Biochemistry, Faculty of Medicine, Gaziantep University, Gaziantep, Türkiye

MD

İbrahim Bozgeyik, Department of Medical Biology, Faculty of Medicine, Adıyaman University, Adıyaman, Türkiye

PhD

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Figure 1. Serum AREG levels in NSCLC patients and healthy controls. Since the resulting data is not normally distributed, statistical analysis was performed using the Mann-Whitney U test. **** p<0.0001.

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Published

2026-02-13

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Duyuran, R., Taşdemir, D., Yumrutaş, P., Güven, H., Kuşdoğan, N., Sav Tunca, Z., Öztuzcu, S., Bozgeyik, E., Işık, A. F., Ulusan, A., Çiçek, H., & Bozgeyik, İbrahim. (2026). Investigating the Relationship Between Serum Amphiregulin Levels and Natural Killer Cell Activity in Patients with Non-Small Cell Lung Cancer and Healthy Individuals. European Journal of Therapeutics. https://doi.org/10.58600/eurjther2848

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Copyright (c) 2026 Rumeysa Duyuran, Demet Taşdemir, Pınar Yumrutaş, Hülya Güven, Nurevşan Kuşdoğan, Zeynep Sav Tunca, Serdar Öztuzcu, Esra Bozgeyik, Ahmet Ferudun Işık, Ahmet Ulusan, Hülya Çiçek, İbrahim Bozgeyik

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