Abstract
PurposeG3BP1 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.MethodsIn 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.ResultsWe 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).ConclusionG3BP1 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.
Highlights
Lung cancer originates from the alveoli and bronchial mucosal epithelium, and is one of the malignant tumors with the highest incidence and mortality in China and the world, which seriously endangers human health.[1,2] Based on the WHO criteria, lung cancer is usually divided into nonsmall cell lung cancer (NSCLC) and small cell lung cancer (SCLC), of which NSCLC accounts for more than 80%.3 Early lung cancer is mostly asymptomatic, and most patients are in advanced stage at the first diagnosis, resulting in a 5‐year survival rate of only about 16% for lung cancer.[4]
The results showed that the mRNA expression of GTase‐activating protein SH3 domain binding protein 1 (G3BP1) and YB1 was significantly higher in NSCLC tissues than that in normal control tissues
We found that G3BP1 was positively correlated with YB1 in mRNA level (r = .399, P < .001; Figure 1)
Summary
Lung cancer originates from the alveoli and bronchial mucosal epithelium, and is one of the malignant tumors with the highest incidence and mortality in China and the world, which seriously endangers human health.[1,2] Based on the WHO criteria, lung cancer is usually divided into nonsmall cell lung cancer (NSCLC) and small cell lung cancer (SCLC), of which NSCLC accounts for more than 80%.3 Early lung cancer is mostly asymptomatic, and most patients are in advanced stage at the first diagnosis, resulting in a 5‐year survival rate of only about 16% for lung cancer.[4]. Ras‐GTase‐activating protein SH3 domain binding protein 1 (G3BP1) is the first RasGAP SH3 domain binding protein isolated through immunoprecipitation by Parker et al,[5] which plays a key role in regulating Ras signal transduction and belongs to RNA‐binding protein family.[6] Its dephosphorylation facilitates the assembly of stress granules (SGs) which maximize the ability of cells to survive to repair stress‐induced changes under stress conditions.[7,8] Y‐box binding protein 1 (YB‐1), an RNA/DNA binding protein, is ubiquitous in prokaryotic and eukaryotic cells, which contains a highly conserved cold shock domain and can bind to the Y‐box sequence in the enhancer and promoter of the target gene.[9] YB1, as a transcription and translation factor, plays the vital role in regulating cell proliferation, differentiation and stress response.[10] Akt, known as protein kinase B (PKB), is a highly conserved threonine/serine protein kinase in evolution It mainly exists in the cytoplasm and acts as a pivotal molecule in activating PI3K/AKT signaling pathway.[11] Phosphorylated protein kinase B (p‐AKT) can regulate many proteins related to cell metabolism, apoptosis, proliferation and differentiation, inhibiting cell apoptosis and promoting the growth of cancer cells.[12] It was reported that YB‐1 could bind to the 5′UTR of G3BP1 transcripts to up‐regulate translation of G3BP1, controlling the validity of the G3BP1 SG nucleator in SG assembly and promoting the tumor progression.[13]. We detected the expression of G3BP1, p‐AKT, and YB1 proteins in 48 cases of noncancerous control lung tissues and 247 cases of NSCLC by IHC and investigate the mRNA level of G3BP1 and YB1, and thereby exploring the relationship between the expression of G3BP1, YB1, and p‐AKT proteins and clinicopathological features and their prognostic significance in NSCLC
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