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Abstract
Ampullary adenocarcinoma is a rare gastrointestinal cancer in which WNT signalling dysregulation has been previously reported. Secreted frizzled related protein 1 (SFRP1) is one of the extracellular ligands of WNT signalling. We performed bioinformatics analyses of SFRP1 expression in human cancer. Microarray analysis of SFRP1 in periampullary adenocarcinoma was obtained from the Gene Expression Omnibus GSE39409 dataset. SFRP1 expression in ampullary adenocarcinoma was detected by immunohistochemistry staining and correlated with patients’ clinical outcomes. Our results showed that SFRP1 expression had different clinical applications in all types of human cancer. No detected alteration of SFPR1 gene and SFRP1 expression in ampullary adenocarcinoma was lower than that in other periampullary adenocarcinomas. However, high expression levels of SFRP1 protein were correlated with cancer recurrence, peritoneal carcinomatosis and poor patient prognosis. Gene set enrichment analysis showed downregulation of multiple WNT-related genes in primary culture cells from ampullary adenocarcinoma, but SFRP1 expression was increased. We found an interaction between WNT, bone morphogenetic protein and hedgehog signalling with SFRP1. Furthermore, a high expression of SFRP1 predicted poor prognosis for ampullary adenocarcinoma patients. Because it is a multifunctional protein, SFRP1 targeting serves as a potential therapy for ampullary adenocarcinoma patients.
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1 Chi-Mei Medical Center, Division of Colorectal Surgery, Department of Surgery, Tainan, Taiwan (GRID:grid.413876.f) (ISNI:0000 0004 0572 9255)
2 National Cheng Kung University, Department of Surgery, National Cheng Kung University Hospital, College of Medicine, Tainan, Taiwan (GRID:grid.64523.36) (ISNI:0000 0004 0532 3255); National Cheng Kung University, Institute of Clinical Medicine, College of Medicine, Tainan, Taiwan (GRID:grid.64523.36) (ISNI:0000 0004 0532 3255)
3 The University of Texas MD Anderson Cancer Center, Department of Gastrointestinal Medical Oncology, Houston, USA (GRID:grid.240145.6) (ISNI:0000 0001 2291 4776)
4 National Cheng Kung University, Department of Biochemistry and Molecular Biology, College of Medicine, Tainan, Taiwan (GRID:grid.64523.36) (ISNI:0000 0004 0532 3255); National Cheng Kung University, Institute of Basic Medical Sciences, College of Medicine, Tainan, Taiwan (GRID:grid.64523.36) (ISNI:0000 0004 0532 3255); Taipei Medical University, Ph.D. Program for Cancer Molecular Biology and Drug Discovery, College of Medical Science and Technology, Taipei, Taiwan (GRID:grid.412896.0) (ISNI:0000 0000 9337 0481); Taipei Medical University, Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei, Taiwan (GRID:grid.412896.0) (ISNI:0000 0000 9337 0481)
5 Nguyen Tat Thanh University, NTT Institute of Hi-Technology, Ho Chi Minh City, Vietnam (GRID:grid.473736.2) (ISNI:0000 0004 4659 3737)
6 Chia-Nan University of Pharmacy and Science, Senior Citizen Service Management, Tainan, Taiwan (GRID:grid.411315.3) (ISNI:0000 0004 0634 2255)
7 National Cheng Kung University, Department of Surgery, National Cheng Kung University Hospital, College of Medicine, Tainan, Taiwan (GRID:grid.64523.36) (ISNI:0000 0004 0532 3255)
8 National Cheng Kung University, Department of Surgery, National Cheng Kung University Hospital, College of Medicine, Tainan, Taiwan (GRID:grid.64523.36) (ISNI:0000 0004 0532 3255); Vanderbilt University Medical Center, Department of Biostatistics, Nashville, USA (GRID:grid.412807.8) (ISNI:0000 0004 1936 9916)
9 National Cheng Kung University, Department of Biochemistry and Molecular Biology, College of Medicine, Tainan, Taiwan (GRID:grid.64523.36) (ISNI:0000 0004 0532 3255); National Cheng Kung University, Institute of Basic Medical Sciences, College of Medicine, Tainan, Taiwan (GRID:grid.64523.36) (ISNI:0000 0004 0532 3255); National Cheng Kung University, Center for Infectious Diseases and Signaling Research, College of Medicine, Tainan, Taiwan (GRID:grid.64523.36) (ISNI:0000 0004 0532 3255)