Abstract
Pancreatic ductal adenocarcinoma (PDAC) is the most lethal cancer in humans, with a 5‐year survival rate of <5%. Recently, glypican‐1 (GPC1)‐expressing circulating exosomes were found to be a promising diagnostic tool for PDAC. However, the aberrant expression of GPC1 has not been systematically evaluated in large‐scale clinical samples of PDAC. Here, we performed a comprehensive analysis of GPC1 mRNA and protein expression features. Included in this study were 178 PDAC patients from the cancer genome atlas (TCGA) and 186 subjects whose tissues were used in immunohistochemical staining assays. We demonstrated that GPC1 mRNA was silenced in normal pancreata; however, it was re‐expressed in PDAC tissues probably because of the promoter hypomethylation. The GPC1 protein was barely expressed in the normal and adjacent noncancerous pancreata. In tumor tissues, 59.7% (111/186) of the detected samples showed positive expression. Notably, GPC1 was elevated in 63.6% (34/55) of early stage cases. High levels of GPC1 were associated with poorer differentiation and larger tumor diameters. Kaplan–Meier analysis showed a significant difference in overall survival between the groups categorized by GPC1 expression (P = 0.0028). Multivariate analyses indicated that GPC1 was a significant risk factor for poor overall survival with a 1.82‐fold increase in the hazard ratio (P = 0.0022). In conclusion, during pancreatic tumorigenesis, GPC1 was ectopically expressed and served as an independent poor prognostic factor. Our findings highlighted the alluring prospect of GPC1 as an early diagnostic and prognostic marker as well as a therapeutic target for PDAC.
Highlights
Pancreatic cancer is the most lethal cancer in humans worldwide
As the predominantly expressed glypican in pancreatic cancer, GPC1 mRNA is associated with worse tumor biological characteristics
According to the the cancer genome atlas (TCGA) RNA sequencing data from pancreatic adenocarcinoma patients (n = 178), we observed that GPC1 is the major expressed form in pancreatic adenocarcinoma among the six glypican family members in the human genome (GPC1-6; Fig. 1A)
Summary
Pancreatic cancer is the most lethal cancer in humans worldwide. Its incidence is ranked 15th among common malignancies [1], only approximately 4% of patients live 5 years after diagnosis [2]. Due to the asymptomatic nature of early-stage pancreatic cancer, approximately 80–85% of cases at initial diagnosis present with unresectable advanced or metastatic disease. The median survival time for these patients is only 3–14 months [2]. Screening or early detection of pancreatic cancer is a promising tool to improve clinical outcome. GPC1 Expression and its Clinical Significance in PDAC
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