TY - JOUR
T1 - Identification of novel lipid metabolic biomarkers associated with poor adrenocortical carcinoma prognosis using integrated bioinformatics
AU - Subramanian, Chitra
AU - Cohen, Mark S.
N1 - This research was funded in part by the National Institutes of Health (R01 CA173292 and R01 CA216919 [M.S.C. and B.S.J.B.], 3U01 CA120458 [M.S.C. and B.S.J.B.]), the University of Michigan Comprehensive Cancer Center Support Grant P30-CA-046592, and the University of Michigan Department of Surgery.
PY - 2022/1
Y1 - 2022/1
N2 - Background: Adrenocortical carcinoma while rare, often presents with advanced metastatic disease carrying a 5-year survival of <15%. Despite adrenocortical carcinoma tumors having high avidity for cholesterol, the role of lipids in adrenocortical carcinoma has not been well described. Therefore, we performed an integrated bioinformatic analysis to identify novel lipid biomarkers correlating with poor survival that may help identify adrenocortical carcinoma tumor progression or therapy resistance. Methods: A meta-analysis of collated adrenocortical carcinoma studies from the correlation engine identified lipid metabolism genes differentially expressed between adrenocortical carcinoma and the normal adrenal, which were then selected for enrichment analysis by the Database for Annotation, Visualization and Integrated Discovery database. A protein-protein interaction network of genes was constructed using Search Tool for the Retrieval of Interacting Genes/Proteins and Cytoscape. Top hub genes identified were validated using the Xena database. Survival analysis of hub genes was performed in the R2 genomic analysis platform using The Cancer Genome Atlas program data set. Results: Examination of pathways by correlation engine identified a unique subset of lipid metabolism-related genes that are differentially regulated in adrenocortical carcinoma tumors versus normal tissues (P < .01). Enrichment pathway analysis in Database for Annotation, Visualization and Integrated Discovery indicated that genes involved in sphingolipid, steroid, and peroxisome proliferator-activated receptor-α metabolism is upregulated in adrenocortical carcinoma, whereas glycerol phospholipid, fatty acid, and phosphatidylinositol metabolism are downregulated. Survival analysis of differentially regulated genes indicated that upregulation of SGPL1, FDFT1, SQLE and downregulation of PIK3C2B, PIK3CD, SYNJ2, DGAT1, PLA2G16, PLD1, GPD1 are all significantly associated with poor overall survival (P < .05) in adrenocortical carcinoma patients. Conclusion: Upregulation of sphingolipid and steroid synthesis genes and downregulation of phosphatidylinositol and glycerol phospholipid metabolism are associated with worse survival in patients with adrenocortical carcinoma.
AB - Background: Adrenocortical carcinoma while rare, often presents with advanced metastatic disease carrying a 5-year survival of <15%. Despite adrenocortical carcinoma tumors having high avidity for cholesterol, the role of lipids in adrenocortical carcinoma has not been well described. Therefore, we performed an integrated bioinformatic analysis to identify novel lipid biomarkers correlating with poor survival that may help identify adrenocortical carcinoma tumor progression or therapy resistance. Methods: A meta-analysis of collated adrenocortical carcinoma studies from the correlation engine identified lipid metabolism genes differentially expressed between adrenocortical carcinoma and the normal adrenal, which were then selected for enrichment analysis by the Database for Annotation, Visualization and Integrated Discovery database. A protein-protein interaction network of genes was constructed using Search Tool for the Retrieval of Interacting Genes/Proteins and Cytoscape. Top hub genes identified were validated using the Xena database. Survival analysis of hub genes was performed in the R2 genomic analysis platform using The Cancer Genome Atlas program data set. Results: Examination of pathways by correlation engine identified a unique subset of lipid metabolism-related genes that are differentially regulated in adrenocortical carcinoma tumors versus normal tissues (P < .01). Enrichment pathway analysis in Database for Annotation, Visualization and Integrated Discovery indicated that genes involved in sphingolipid, steroid, and peroxisome proliferator-activated receptor-α metabolism is upregulated in adrenocortical carcinoma, whereas glycerol phospholipid, fatty acid, and phosphatidylinositol metabolism are downregulated. Survival analysis of differentially regulated genes indicated that upregulation of SGPL1, FDFT1, SQLE and downregulation of PIK3C2B, PIK3CD, SYNJ2, DGAT1, PLA2G16, PLD1, GPD1 are all significantly associated with poor overall survival (P < .05) in adrenocortical carcinoma patients. Conclusion: Upregulation of sphingolipid and steroid synthesis genes and downregulation of phosphatidylinositol and glycerol phospholipid metabolism are associated with worse survival in patients with adrenocortical carcinoma.
UR - http://www.scopus.com/inward/record.url?scp=85111739633&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85111739633&partnerID=8YFLogxK
U2 - 10.1016/j.surg.2021.04.049
DO - 10.1016/j.surg.2021.04.049
M3 - Article
C2 - 34353633
AN - SCOPUS:85111739633
SN - 0039-6060
VL - 171
SP - 119
EP - 129
JO - Surgery (United States)
JF - Surgery (United States)
IS - 1
ER -