Glypican-3 is overexpressed in lung squamous cell carcinoma, but not in adenocarcinoma

Abstract

Glypican-3 is a membrane-bound proteoglycan whose expression has been linked to malignancies through the existence of both mutations and aberrant protein expression. Reports on glypican-3 expression in lung cancer were limited, with some evidence for loss of expression, which suggested a tumor-suppressor role. We sought to evaluate glypican-3 expression in lung cancer at the protein and mRNA levels and correlate it with clinical, histological and genomic characteristics such as RAS mutation status. We used immunohistochemistry on tissue microarray to study glypican-3 expression in 97 patients, evaluated glypican-3 mRNA levels by quantitative polymerase chain reaction in 143 patients and identified RAS mutations by allele-specific oligonucleotide hybridization. We correlated the results with clinical and histological data. Glypican-3 immunostaining was negative in all normal lung tissues, but positive in 23% of lung carcinoma samples. High protein and mRNA expression was associated with squamous histology (positive stain in 55% of squamous cell carcinoma vs 8% of adenocarcinoma, Po0.0001 for both immunostaining and mRNA). RAS mutations were highly associated with adenocarcinoma and low glypican-3 mRNA expression (Po0.0001 for both). Among smokers, glypican-3 mRNA expression was reduced in adenocarcinoma patients (P ¼ 0.013), and was elevated in those with squamous cell carcinoma (P ¼ 0.03, interaction P ¼ 0.0009). These opposing associations also correlated with the smoking burden. Patients with tumors staining positively for glypican-3 smoked significantly more than patients with tumors staining negatively (P ¼ 0.013). No association was found between glypican-3 expression and patient outcome. In conclusion, glypican-3 was overexpressed in cancerous compared with normal lung tissue. Adenocarcinoma and squamous cell carcinoma had differential expression of glypican-3, with predilection to squamous cell carcinoma patients who smoked. Glypican-3 expression in squamous cell carcinoma as an oncofetal protein renders it a potential candidate marker for early detection of lung squamous cell carcinoma.

Differential expression of glypican-3 (GPC3) in lung squamous cell carcinoma and lung adenocarcinoma and its clinical significance

“…Through interactions with the extracellular matrix, cell growth factors, and proteases, GPC3 regulates the proliferation, differentiation, adhesion, and metastasis of the tumor cells. The amino terminus of GPC3 is also observed in the soluble form of the GPC3 protein, which can be secreted into the peripheral blood by tissues and cells (Aviel-Ronen et al, 2008). Recent studies have confirmed that GPC3 is closely related to the development, progression, and prognosis of malignant tumors, such as hepatocellular carcinoma, and may serve as a valuable tumor marker for the early diagnosis of hepatocellular carcinoma (Magistri et al, 2013).…”

Glypican-3 expression in clear cell adenocarcinoma of the ovary

“…[16][17][18] GPC3 expression, ubiquitous in the embryo, is silenced in most adult tissues, 19,20 and is regarded, therefore, as an oncofetal protein. Its overexpression has been reported in certain types of tumors, such as hepatocellular carcinoma, 21,22 melanoma, 23 lung squamous cell carcinoma, 24 and testicular germ cell tumors. 25,26 GPC3 has also been reported to act as an immunohistochemical and serum marker for hepatocellular carcinoma and malignant melanoma.…”

Screening and Identification of Distant Metastasis‐Related Differentially Expressed Genes in Human Squamous Cell Lung Carcinoma

“…High-throughput microarray technology facilitates simultaneous analysis of gene expressions and identification of numerous differentially expressed genes (Khan et al, 1999;Ross et al, 2000;Tanney et al, 2008). Using this technique, many studies have been done to determine the metastatic information of individual genes (Marchetti et al, 2002;Aviel-Ronen et al, 2008), cell lines with different invasive activities (Xu et al, 2008;Li et al, 2010), and differences between the primary tumors and normal lung tissues in gene expression level (Heighway et al, 2002). However, the metastasis-related pathological alternations in a molecular level have not been well studied.…”