The clinical significance and function of EGFR mutation in TKI treatments of NSCLC patients

Article type: Research Article

Authors: Ding, Hao^a | Chen, Yuxing^a | Zhao, Yuanyang^a | Zhu, Li^{b; *} | Huang, Huaying^a | Liu, Chenyang^a | Zhang, Feng^c | Zhang, Cunxi^d | Jin, Cheng^e

Affiliations: [a] Division of Respiratory Disease, Affiliated People’s Hospital of Jiangsu University, Zhenjiang, Jiangsu, China | [b] Division of Nephrology, Affiliated People’s Hospital of Jiangsu University, Zhenjiang, Jiangsu, China | [c] Division of Respiratory Disease, Zhenjiang First People’s Hospital Branch, Zhenjiang, Jiangsu, China | [d] Division of Thoracic Surgery, Zhenjiang First People’s Hospital Branch, Zhenjiang, Jiangsu, China | [e] Department of Geriatrics, Affiliated People’s Hospital of Jiangsu University, Zhenjiang, Jiangsu, China

Correspondence: [*] Corresponding author: Li Zhu, Division of Nephrology, Affiliated People’s Hospital of Jiangsu University, Dianli Road No. 8, Zhenjiang, Jiangsu 212002, China. Tel.: +86 15951271160; Fax: +86 511 88915367; E-mail: [email protected].

Abstract: BACKGROUND: EGFR mutations widely exists in NSCLC patients, which are involved in cancer development. OBJECTIVE: The function of EGFR mutations in the resistance to TKI treatments of NSCLC was evaluated to provide theoretical support for the clinical management of NSCLC patients. METHODS: A total of 150 NSCLC patients including 118 patients with EGFR mutation and 32 without, were included in this study. The EGFR mutation status and subtypes were analyzed in recruited patients. The distribution of EGFR mutation subtypes and their association with clinicopathological features were also assessed. The prognostic value of EGFR mutation was evaluated by the overall survival of recruited patients. The function of EGFR mutation was estimated, in vitro, in the TKI resistant NSCLC cells with different subtypes of EGFR mutation. RESULTS: The exon 19 deletion was the most common subtype of EGFR mutation in the enrolled patients followed by the exon 21 L858R point mutation. The EGFR mutations were closely associated with the differentiation degree and the histological types of NSCLC cases. EGFR mutation was an independent prognostic factor of NSCLC with a close relationship with the overall survival of patients. The exon 20 T790M mutation results in the erlotinib resistance through the PI3K/Akt signaling pathway. CONCLUSIONS: The EGFR mutation is a critical factor in the prognosis and for the resistance to TKI treatment in NSCLC. The exon 20 T790M mutation was involved in the erlotinib resistance through PI3K/Akt signaling pathway.

Keywords: EGFR mutation, NSCLC, TKI-resistance, erlotinib, serum, exon 20

DOI: 10.3233/CBM-210281

Journal: Cancer Biomarkers, vol. 35, no. 1, pp. 119-125, 2022