GPC3 affects the prognosis of lung adenocarcinoma and lung squamous cell carcinoma

Abstract

Background Glypican 3 (GPC3) is a heparin sulphate proteoglycan whose expression is associated with several malignancies. However, its expression in non-small-cell lung carcinoma (NSCLC) is limited and ambiguous. This study aimed to comprehensively evaluate the expression of GPC3 in NSCLC and develop a risk-score model for predicting the prognosis of NSCLC. Methods The gene expression profiles of lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) were downloaded from the UCSC Xena database. Using the limma package, the differentially expressed genes (DEGs) between different comparison groups were analysed and the differential expression of GPC3 was calculated. A functional enrichment analysis was conducted for GPC3-associated genes using the DAVID tool. For the GPC3-associated genes shared by the four comparison groups, a protein–protein interaction network was built using the Cytoscape software. After conducting a survival analysis and a Cox regression analysis, the genes found to be significantly correlated with prognosis were selected to construct a risk-score model. Besides, the gene and protein levels of GPC3 were examined by quantitative reverse transcriptase-PCR (qRT-PCR) and immunohistochemistry (IHC) in LUSC tissues and paracancer tissues. Results The differential expression of GPC3 was significant (adjusted P < 0.05) in the NSCLC vs. normal, LUAD vs. normal, LUSC versus normal, and LUAD versus. LUSC comparison groups. GPC3 directly interacted with SERPINA1, MFI2, and FOXM1. Moreover, GPC3 expression was significantly correlated with pathologic N, pathologic T, gender, and tumour stage in LUAD samples. Finally, the risk-score model (involving MFI2, FOXM1, and GPC3) for LUAD and that (involving SERPINA1 and FOXM1) for LUSC were established separately. The qRT-PCR result showed that GPC3 expression was much higher in the LUSC tissues than that in the normal group. The IHC results further showed that GPC3 is highly expressed in LUSC tissues, but low in paracancer tissues. Conclusion The three-gene risk-score model for LUAD and the two-gene risk-score model for LUSC might be valuable in improving the prognosis of these carcinomas.

Identification of Inflammatory Response-Related Gene Signature Associated With Immune Status and Prognosis of Lung Adenocarcinoma

“… Kim et al (2003) demonstrated GPC3 to be a candidate gene for lung tumor suppression. Ning et al (2021) found GPC3 expression was significantly correlated with gender and tumour stage in LUAD samples. IL7R has been explored as aggressive tumor features for patients with LUAD: KRAS mutation, larger tumor size, lymphovascular invasion, high-grade morphology, and more frequent recurrence ( Suzuki et al, 2013 ).…”

Analysis and identification of potential key genes in hepatic ischemia-reperfusion injury

“…GPC3 is highly expressed during the fetal period, and its expression level is reduced after birth. GPC3 is overexpressed in hepatocellular carcinoma (HCC), embryonal tumors, melanoma, and some germ cell tumors, and is closely related to tumorigenesis and prognosis ( 32 , 33 ). These key genes play an important role in a variety of diseases, but their function in HIRI is still unknown.…”

Glypican 3 (GPC 3) In Cancer Pathogenesis and Progression

“…These findings suggest that GPC 3 may be a lung tumour suppressor gene that is downregulated by tobacco exposure [97,98]. However, GPC 3 expression has been described in several lung squamous cell carcinomas (LSCC) [21,26,27]. A study by Kim et al investigated GPC 3 expression and its role in lung cancer [97].…”

“…GPC 3 expression is also upregulated in most embryonic tissue, such as placenta and liver, but downregulated in the adult tissue of corresponding organ (Figure 3) [11]. In these tissues, GPC 3 expression is predominantly observed during development, with expression peaking in-utero before downregulation after birth [16,21,27]. Hence, this suggests the important role of GPC 3 in developmental morphogenesis [28].…”