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ORIGINAL RESEARCH article

Front. Oncol.
Sec. Thoracic Oncology
Volume 15 - 2025 | doi: 10.3389/fonc.2025.1434249

Role of guanylate-binding protein 1 in the proliferation of invasive lung adenocarcinoma cells

Provisionally accepted
Takashi Kumada Takashi Kumada Takahiro Mimae Takahiro Mimae *Norifumi Tsubokawa Norifumi Tsubokawa *Kei Kushitani Kei Kushitani Yukio Takeshima Yukio Takeshima Yoshihiro Miyata Yoshihiro Miyata Morihito Okada Morihito Okada *
  • Hiroshima University, Hiroshima, Japan

The final, formatted version of the article will be published soon.

    Guanylate-binding protein 1 (GBP1) is involved in the malignant progression of lung adenocarcinoma, particularly in the acquisition of invasive potential. However, its role in tumor proliferation and therapeutic viability in invasive lung adenocarcinomas remains unclear.This study included 99 patients with invasive lung adenocarcinoma, excluding those with noninvasive lepidic components, who had undergone complete pulmonary resection. Immunohistochemical staining was performed to examine the presence of GBP1, and its prognostic significance was assessed using uni-and multi-variable Cox regression analyses. Additionally, the expression levels of GBP1 gene and protein levels were evaluated in lung adenocarcinoma cell lines (PC-9, A549, NCI-H322, NCI-H441, NCI-H820, and ABC-1), and its proliferative role in these cell lines was analyzed using specific inhibitors targeting GBP1. GBP1 expression was detected in 45 (45.5%) patients. The 5-year overall survival rates for GBP1positive and -negative patients were 66.0% (95% confidence interval (CI): 46.3-80.0%) and 85.7% (95% CI: 72.0-93.0%), respectively (P = 0.029). The multivariable analysis demonstrated that GBP1 positivity was an independent factor for poor overall survival (hazard ratio [HR] = 2.52 [95% CI: 1.02-6.22], P = 0.045). GBP1 gene and protein were markedly expressed in NCI-H820 than in NCI-H322 and ABC-1. The inhibitor targeting GBP1 significantly suppressed the growth of NCI-H820 but not that of NCI-H322 or ABC-1.GBP1 is a prognostic factor that may be involved in the proliferation of invasive lung adenocarcinoma, suggesting that inhibiting GBP1 activity may be a promising therapeutic approach for lung adenocarcinoma patients expressing GBP1.

    Keywords: Gbp11, Lung adenocarcinoma2, Prognostic factor3, inhibitor4, cell growth5, therapy6

    Received: 17 May 2024; Accepted: 03 Jan 2025.

    Copyright: © 2025 Kumada, Mimae, Tsubokawa, Kushitani, Takeshima, Miyata and Okada. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Takahiro Mimae, Hiroshima University, Hiroshima, Japan
    Norifumi Tsubokawa, Hiroshima University, Hiroshima, Japan
    Morihito Okada, Hiroshima University, Hiroshima, Japan

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