Document Type : Original Article(s)
Authors
1 Department of Radiation Oncology, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
2 Department of Respiratory Medicine, Regional Medical Center for the National Institute of Respiratory Disease, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China
Abstract
Background: Targeted drug resistance is a bottleneck in lung cancer treatment. The present study aimed to explore the role of insulin-like growth factor-binding protein 7 (IGFBP7) in epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) acquired resistance.
Method: A retrospective case-control study was conducted in-vitro on cell lines. Cell lines experiments in-vitro and Stable resistant strains of PC9 cells were selected under 5μM gefitinib. IGFBP7 and the related insulin-like growth factor-1 receptor (IGF-1R)/insulin receptor (IR) signaling pathway proteins were detected by western blot. SiRNA interference was used to downregulate IGFBP7 level in the PC9-Gefitinib resistant (PC9-GR) cells. Cell proliferation assay and invasion assay were carried out. The serum level of IGFBP7 and insulin was detected in EGFR-TKI acquired resistant and EGFR-TKI sensitive patients. Quantitative data was expressed as mean ± standard deviation values. Chi-square test was used to compare the baseline clinical characteristics of the patients. One-way analysis of variance was used to detect the differences between groups. A P-value<0.05 was considered statistically significant.
Results: The upregulation of IGFBP7, Tyr1135/1136, IR-β, IRS1 and IGF-1R protein was observed. The interference of IGFBP7 slowed down the proliferation rate and weakened the invasion ability of PC9-GR cells. The EGFR-TKI resistant subgroup analysis according to the T790 mutation (T790M) status suggested that IGFBP7’s concentration in the T790M negative group was significantly higher than that in the T790M positive group (53.21 ± 49.15 versus 14.37 ± 0.78, P < 0.05).
Conclusion: IGFBP7 and insulin-IGF-1R-IR network contributed to EGFR-TKI acquired resistance. IGFBP7 functioned both in T790M positive and T790M negative EGFR-TKI acquired resistance.
Keywords
- Insulin-like growth factor binding protein-related protein 1
- Targeted drug resistance
- Lung neoplasms
Main Subjects
Please cite this article as: Hu Q, Ruan W, Zhu H, Yan C, Xu Y. The Role of IGFBP7 in EGFR-TKI Acquired Resistant Lung Cancer. Middle East J Cancer. 2026: in press. doi: 10.30476/mejc.2026.107427.2290.
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