An Analysis of G3BP2 in Non-Small Cell Lung Cancer

Cancer cells are subjected to various stress conditions and have stress adaptability strategies to survive. Various types of stresses lead to the aggregation of cytoplasmic RNA granules known as stress granules (SGs), seen in normal and tumor cells, and aid in cell survival by avoiding cell apoptosis. G3BP stress granule assembly factor 2 (G3BP2) encodes a multifunctional protein with known roles as a critical component of SGs and is also associated with chemoresistance in cancer, but its known roles in non-small cell cancer (NSCLC) are limited.

We evaluated the expression of G3BP2 via qPCR and immunohistochemistry on a retrospective cohort of NSCLC isolated at surgery in St James's Hospital, Dublin, Ireland. Expression levels were correlated with clinicopathological parameters. Survival analyses, including Kaplan-Meier analyses, were used to determine the prognostic value. Additional correlations with other available NSCLC datasets were explored.

In contrast to other studies, we did not observe upregulated expression of G3BP2. Furthermore, Kaplan-Meier analyses did not identify any prognostic value associated with G3BP2 expression in patient tissues in contrast to other published data. Bioinformatic analyses on these other datasets found strong correlations between G3BP2 and core stress granule genes in NSCLC. Additional analyses also identified correlations between G3BP2 expression and immune cell infiltration, immune cell exhaustion, and DNA Damage Response pathways. An examination of the available datasets did not find any overall prognostic value for altered DNA methylation and survival. However, two individual CpG residues were identified for which higher methylation was associated with worse overall survival. Finally, the effects of a G3BP2 inhibitor on cellular proliferation were assessed.

In our analysis, G3BP2 was not associated with survival benefit. However, clear associations were observed between altered expression of this gene and a number of important pathways linked to cancer pathogenesis, and further studies are warranted to assess this gene (and/or) stress granules in cancer.