TY - JOUR
T1 - Upregulation of peroxisome proliferator-activated receptor-α and the lipid metabolism pathway promotes carcinogenesis of ampullary cancer
AU - Wang, Chih Yang
AU - Chao, Ying Jui
AU - Chen, Yi Ling
AU - Wang, Tzu Wen
AU - Phan, Nam Nhut
AU - Hsu, Hui Ping
AU - Shan, Yan Shen
AU - Lai, Ming Derg
N1 - Funding Information:
Bioinformatics analyses and data mining were conducted at Taipei Medical University and the Bioinformatics Core at National Cheng Kung University. The authors give special thanks to Mr. Dan Chamberlin for his professional English editing at the Office of Research and Development at Taipei Medical University. The authors are grateful for the support from the Human Biobank, Research Center of Clinical Medicine, National Cheng Kung University Hospital. We are blessed with support from the late superintendent, Professor Pin-wen Lin. Furthermore, we thank Miss Ya-Li Hsiao for technical support. The study was supported by the Ministry of Science and Technology (MOST) of Taiwan (grants MOST105-2325-B-006-003 to M-D. L., MOST 108-2314-B-006-082 to H-P. H., and MOST109-2320-B-038-009-MY2 to C-Y.W.), and Taipei Medical University (grant TMU-108-AE1-B16 to C-Y. W.).
Funding Information:
Bioinformatics analyses and data mining were conducted at Taipei Medical University and the Bioinformatics Core at National Cheng Kung University. The authors give special thanks to Mr. Dan Chamberlin for his professional English editing at the Office of Research and Development at Taipei Medical University. The authors are grateful for the support from the Human Biobank, Research Center of Clinical Medicine, National Cheng Kung University Hospital. We are blessed with support from the late superintendent, Professor Pin-wen Lin. Furthermore, we thank Miss Ya-Li Hsiao for technical support. The study was supported by the Ministry of Science and Technology (MOST) of Taiwan (grants MOST 105-2325-B-006-003 to M-D. L., MOST 108-2314-B-006-082 to H-P. H., and MOST 109-2320-B-038-009-MY2 to C-Y.W.), and Taipei Medical University (grant TMU-108-AE1-B16 to C-Y. W.).
Publisher Copyright:
© The author(s).
PY - 2021
Y1 - 2021
N2 - Ampullary cancer is a rare periampullary cancer currently with no targeted therapeutic agent. It is important to develop a deeper understanding of the carcinogenesis of ampullary cancer. We attempted to explore the characteristics of ampullary cancer in our dataset and a public database, followed by a search for potential drugs. We used a bioinformatics pipeline to analyze complementary (c)DNA microarray data of ampullary cancer and surrounding normal duodenal tissues from five patients. A public database from the National Center for Biotechnology Information Gene Expression Omnibus (NCBI GEO) was applied for external validation. Bioinformatics tools used included the Gene Set Enrichment Analysis (GSEA), Database for Annotation, Visualization and Integrated Discovery (DAVID), MetaCore, Kyoto Encyclopedia of Genes and Genomes (KEGG), Hallmark, BioCarta, Reactome, and Connectivity Map (CMap). In total, 9097 genes were upregulated in the five ampullary cancer samples compared to normal duodenal tissues. From the MetaCore analysis, genes of peroxisome proliferator-activated receptor alpha (PPARA) and retinoid X receptor (RXR)-regulated lipid metabolism were overexpressed in ampullary cancer tissues. Further a GSEA of the KEGG, Hallmark, Reactome, and Gene Ontology databases revealed that PPARA and lipid metabolism-related genes were enriched in our specimens of ampullary cancer and in the NCBI GSE39409 database. Expressions of PPARA messenger (m)RNA and the PPAR-α protein were higher in clinical samples and cell lines of ampullary cancer. US Food and Drug Administration (FDA)-approved drugs, including alvespimycin, trichostatin A (a histone deacetylase inhibitor), and cytochalasin B, may have novel therapeutic effects in ampullary cancer patients as predicted by the CMap analysis. Trichostatin A was the most potent agent for ampullary cancer with a half maximal inhibitory concentration of < 0.3 µM. According to our results, upregulation of PPARA and lipid metabolism-related genes are potential pathways in the carcinogenesis and development of ampullary cancer. Results from the CMap analysis suggested potential drugs for patients with ampullary cancer.
AB - Ampullary cancer is a rare periampullary cancer currently with no targeted therapeutic agent. It is important to develop a deeper understanding of the carcinogenesis of ampullary cancer. We attempted to explore the characteristics of ampullary cancer in our dataset and a public database, followed by a search for potential drugs. We used a bioinformatics pipeline to analyze complementary (c)DNA microarray data of ampullary cancer and surrounding normal duodenal tissues from five patients. A public database from the National Center for Biotechnology Information Gene Expression Omnibus (NCBI GEO) was applied for external validation. Bioinformatics tools used included the Gene Set Enrichment Analysis (GSEA), Database for Annotation, Visualization and Integrated Discovery (DAVID), MetaCore, Kyoto Encyclopedia of Genes and Genomes (KEGG), Hallmark, BioCarta, Reactome, and Connectivity Map (CMap). In total, 9097 genes were upregulated in the five ampullary cancer samples compared to normal duodenal tissues. From the MetaCore analysis, genes of peroxisome proliferator-activated receptor alpha (PPARA) and retinoid X receptor (RXR)-regulated lipid metabolism were overexpressed in ampullary cancer tissues. Further a GSEA of the KEGG, Hallmark, Reactome, and Gene Ontology databases revealed that PPARA and lipid metabolism-related genes were enriched in our specimens of ampullary cancer and in the NCBI GSE39409 database. Expressions of PPARA messenger (m)RNA and the PPAR-α protein were higher in clinical samples and cell lines of ampullary cancer. US Food and Drug Administration (FDA)-approved drugs, including alvespimycin, trichostatin A (a histone deacetylase inhibitor), and cytochalasin B, may have novel therapeutic effects in ampullary cancer patients as predicted by the CMap analysis. Trichostatin A was the most potent agent for ampullary cancer with a half maximal inhibitory concentration of < 0.3 µM. According to our results, upregulation of PPARA and lipid metabolism-related genes are potential pathways in the carcinogenesis and development of ampullary cancer. Results from the CMap analysis suggested potential drugs for patients with ampullary cancer.
UR - http://www.scopus.com/inward/record.url?scp=85097400834&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85097400834&partnerID=8YFLogxK
U2 - 10.7150/ijms.48123
DO - 10.7150/ijms.48123
M3 - Article
C2 - 33390794
AN - SCOPUS:85097400834
SN - 1449-1907
VL - 18
SP - 256
EP - 269
JO - International Journal of Medical Sciences
JF - International Journal of Medical Sciences
IS - 1
ER -