Abstract
Despite improvements reported in diagnosis and treatments in recent decades, pancreatic cancer is still characterized by poor prognosis and low survival rate among solid tumors. Intensive interests have grown in exploring novel predictive biomarkers, aiming to enhance the efficiency in early detection and treatment prognosis. In this study, we identified the differentially expressed genes (DEGs) in pancreatic cancer by analyzing five gene expression profiles and established the functional modules according to the functional interaction (FI) network between the DEGs. A significant upregulation of the selected DEG, interferon (IFN)-induced transmembrane protein 1 (IFITM1), was evaluated in several bioinformatics online tools and verified with immunohistochemistry staining from samples of 90 patients with pancreatic cancer. Prognostic data showed that high expression of IFITM1 associated with poor survival, and multivariate Cox regression analysis showed IFITM1 was one of the independent prognostic factors for overall survival. Meanwhile, significant correlations of the expression of IFITM1 and the infiltration of immune cells were found by TIMER. Furthermore, a higher level of IFITM1 was assessed in pancreatic cancer cell lines compared to normal human pancreatic duct epithelial cells, and silencing IFITM1 in tumor cells remarkedly inhibited cancer tumorigenicity. Collectively, our findings suggested that IFITM1 might have promising utility for pancreatic cancer.
Highlights
Pancreatic cancer is expected to be the second leading cause of cancer-related deaths in developed countries by 2030, and is characterized as highly invasive and metastatic as well as extremely resistant to chemo-radio-therapy [1]
We investigated gene expression profiles from Gene Expression Omnibus (GEO) repository to screen out common differentially expressed genes (DEGs) between pancreatic cancer and normal pancreatic tissues and analyzed them by establishing a protein functional interaction (FI) network
Our study suggested that IFN-induced transmembrane protein 1 (IFITM1) may have promising clinical utility for prognostic stratification, and combining IFITM1 expression profiles systematically with clinical characteristics of patients is promising to be effective for developing treatment
Summary
Pancreatic cancer is expected to be the second leading cause of cancer-related deaths in developed countries by 2030, and is characterized as highly invasive and metastatic as well as extremely resistant to chemo-radio-therapy [1]. IFITM1 in Pancreatic Cancer prognosis, better identification of clinical biomarkers useful for making therapeutic decisions and developing targets for innovative drugs are urgently needed in this complex and heterogeneous mutational landscape. The human interferon (IFN)-induced transmembrane protein 1 (IFITM1), named Leu or CD225, is a 17-kDa cellsurface membrane protein in the IFN-stimulated genes (ISGs) protein family along with IFITM2 and IFITM3. Since it was first discovered in neuroblastoma cells in 1984, it has been identified participating in various biological processes (BPs) including cell proliferation and adhesion and being important in immunity and antiviral activities [4, 5]. It is very likely that IFITM1 may hold hitherto undiscovered value in pancreatic cancer and might be further associated with prognosis of patients with pancreatic cancer
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