Elevated expression of G3BP1 associates with YB1 and p-AKT and predicts poor prognosis in nonsmall cell lung cancer patients after surgical resection

Cancer Med. 2019 Nov;8(16):6894-6903. doi: 10.1002/cam4.2579. Epub 2019 Sep 27.


Purpose: G3BP1 is an RNA-binding protein and plays roles in regulating signaling pathway. YB-1 is a DNA/RNA binding protein encoded by YBX1 gene. Phosphorylated AKT (p-AKT) acts as a pivotal molecule in PI3K/AKT pathway. YB-1 drives stress granules (SGs) formation by activating G3BP1 translation under diverse conditions. SGs are involved in many different metabolic and signaling pathways which may include PI3K/AKT/mTOR. So far, there has been no report on the relationship between expression of G3BP1, p-AKT, and YB1 and clinicopathological features/prognosis in surgically resected nonsmall cell lung cancer (NSCLC) patients.

Methods: In this study, data from TCGA (The Cancer Genome Atlas) were downloaded to investigate the mRNA expression of G3BP1 and YB1 (YBX1) and their correlation in NSCLC. Also, expression of G3BP1, YB1, and p-AKT proteins was studied using immunohistochemistry in tissue microarrays of NSCLC and in noncancerous lung tissues.

Results: We found that the mRNA expression of G3BP1 and YB1 was higher in NSCLC tissues (both P < .05), and G3BP1 was positively correlated with YB1 in mRNA level (r = .399, P < .001). Also, expression of G3BP1, YB1, and p-AKT proteins was higher in NSCLC tissues (all P < .05). And higher expression of G3BP1 and YB1 proteins was seen in patients with clinical stage II and III compared with stage I (both P < .05). Besides, expression of G3BP1 protein had a positive correlation with YB1 and p-AKT (both P < .05). Moreover, overall survival was shorter in patients with overexpression of G3BP1, YB1, and p-AKT proteins (all P < .05). Multivariate analysis confirmed that overexpression of G3BP1 protein was an independent poorer prognostic factor for NSCLC patients (P = .039).

Conclusion: G3BP1 may play a crucial role in activating PI3K/AKT/mTOR pathway. G3BP1 might be served as a novel prognostic biomarker for surgically resected NSCLC patients, which afforded new insights into the study on the mechanism and therapy of NSCLC.

Keywords: G3BP1; YB1; biomarker; nonsmall cell lung cancer; p-AKT; prognosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers / metabolism
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / metabolism
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Carcinoma, Non-Small-Cell Lung / surgery
  • DNA Helicases / genetics*
  • DNA Helicases / metabolism
  • Female
  • Humans
  • Lung / metabolism
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology
  • Lung Neoplasms / surgery
  • Male
  • Middle Aged
  • Poly-ADP-Ribose Binding Proteins / genetics*
  • Poly-ADP-Ribose Binding Proteins / metabolism
  • Prognosis
  • Proto-Oncogene Proteins c-akt / metabolism*
  • RNA Helicases / genetics*
  • RNA Helicases / metabolism
  • RNA Recognition Motif Proteins / genetics*
  • RNA Recognition Motif Proteins / metabolism
  • Y-Box-Binding Protein 1 / genetics*
  • Y-Box-Binding Protein 1 / metabolism


  • Biomarkers
  • Poly-ADP-Ribose Binding Proteins
  • RNA Recognition Motif Proteins
  • Y-Box-Binding Protein 1
  • YBX1 protein, human
  • Proto-Oncogene Proteins c-akt
  • DNA Helicases
  • G3BP1 protein, human
  • RNA Helicases