TY - JOUR
T1 - The influence of depression on ovarian cancer
T2 - Discovering molecular pathways that identify novel biomarkers and therapeutic targets
AU - Rahman, Md Rezanur
AU - Islam, Tania
AU - Al-Mamun, Md Abdullah
AU - Zaman, Toyfiquz
AU - Karim, Md Rezaul
AU - Moni, Mohammad Ali
N1 - Publisher Copyright:
© 2019
PY - 2019/7
Y1 - 2019/7
N2 - Depressive illness is a significant risk factor for ovarian cancer development (OC). The underlying mechanism is unclear (perhaps involving altered neuroendocrine factors), but identifying associated alterations in gene expression of OC in depression sufferers may uncover novel factors that affect OC progression. We thus analyzed microarray gene expression data from OC tissue taken from patients diagnosed with and without depression. We identified 34 differentially expressed genes (DEGs) of depression from OC patients. Gene ontology (GO) and KEGG pathway analyses indicated several molecular pathways including complement and coagulation cascades, the hippo signaling pathway, ether lipid metabolism, the MAPK signaling pathway, and antigen processing and presentation were overrepresented among DEGs. Subsequent, protein-protein interaction (PPI) analysis revealed pathway hub proteins (FOS, EGR1, JUNB, HSPA1B, FGFR3, TRIB1, CTSB, SERPINE1), regulatory transcription factors (TFs; FOS, EGR1, JUNB) and one miRNA, miR-101-5p from TFs-miRNAs coregulatory networks. The prognostic survival analysis of the DEGs revealed CXCL12, ARL4C, NQO2 associated with worse OC survival outcomes. Protein-metabolite interaction network analysis showed that upregulated protein CHPT1 (a choline phosphotransferase) interacts with four important phospholipid synthesis and signaling metabolites. Protein-drug interaction analysis revealed SERPINE1 and PLAT proteins interact with compounds that include thrombolytic drugs, plasmin inhibitors, thiazolidinediones, NSAIDs, and hypertension treatments. Thus, we identified evidence for factors and pathways altered in OC tissue when patient depression is evident, and characterized important aspects of these OC-depression links that may be instrumental in developing new treatments for OC patients.
AB - Depressive illness is a significant risk factor for ovarian cancer development (OC). The underlying mechanism is unclear (perhaps involving altered neuroendocrine factors), but identifying associated alterations in gene expression of OC in depression sufferers may uncover novel factors that affect OC progression. We thus analyzed microarray gene expression data from OC tissue taken from patients diagnosed with and without depression. We identified 34 differentially expressed genes (DEGs) of depression from OC patients. Gene ontology (GO) and KEGG pathway analyses indicated several molecular pathways including complement and coagulation cascades, the hippo signaling pathway, ether lipid metabolism, the MAPK signaling pathway, and antigen processing and presentation were overrepresented among DEGs. Subsequent, protein-protein interaction (PPI) analysis revealed pathway hub proteins (FOS, EGR1, JUNB, HSPA1B, FGFR3, TRIB1, CTSB, SERPINE1), regulatory transcription factors (TFs; FOS, EGR1, JUNB) and one miRNA, miR-101-5p from TFs-miRNAs coregulatory networks. The prognostic survival analysis of the DEGs revealed CXCL12, ARL4C, NQO2 associated with worse OC survival outcomes. Protein-metabolite interaction network analysis showed that upregulated protein CHPT1 (a choline phosphotransferase) interacts with four important phospholipid synthesis and signaling metabolites. Protein-drug interaction analysis revealed SERPINE1 and PLAT proteins interact with compounds that include thrombolytic drugs, plasmin inhibitors, thiazolidinediones, NSAIDs, and hypertension treatments. Thus, we identified evidence for factors and pathways altered in OC tissue when patient depression is evident, and characterized important aspects of these OC-depression links that may be instrumental in developing new treatments for OC patients.
KW - Biomarker signatures
KW - Depression
KW - Differentially expressed genes
KW - Drug targets
KW - Ovarian cancer
KW - Protein-drug interactions
KW - Protein-metabolite interaction
KW - Protein-protein interaction
KW - Survival analysis
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U2 - 10.1016/j.imu.2019.100207
DO - 10.1016/j.imu.2019.100207
M3 - Article
AN - SCOPUS:85069002025
SN - 2352-9148
VL - 16
SP - 1
EP - 8
JO - Informatics in Medicine Unlocked
JF - Informatics in Medicine Unlocked
M1 - 100207
ER -
