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Status |
Public on May 02, 2018 |
Title |
Patient- and Cell Type-Specific Heterogeneity of Metformin Response. |
Organism |
Homo sapiens |
Experiment type |
Expression profiling by array
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Summary |
Most FDA approved drugs are not equally effective in all patients, suggesting that identification of biomarkers to predict responders to a chemoprevention agent will be needed to stratify patients and achieve maximum benefit. The goal of this study was to investigate both patient specific and cell-context specific heterogeneity of metformin response, using cancer cell lines fibroblast cell lines and induced pluripotent stem cells differentiated into lung epithelial lineages. We performed transcriptome analysis on both patient-derived fibroblast cell lines and cancer cell lines to assess differential metformin response and identify response genes. We found differences in response to metformin treatment across a variety of cell lines and cellular contexts, suggesting heterogeneity that may be patient and cell-type specific. Gene expression profiling and analysis of metformin sensitive and resistant cells identified differentially expressed genes that may be able to stratify patients into metformin responders and non-responders.
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Overall design |
Patient derived fibroblast cells, differentiated IPS cells and cancer cells were each treated with their respective IC50 concentrations of metformin and DMSO for 72 hours. Total RNA was extracted, hybridized to the Affymetrix Gene Chip Human Genome U133 Plus 2.0 single arrays and using GeneChip Scanner 3000. Principle Component Analysis (PCA) and unsupervised hierarchical clustering were used to perform quality checks on the samples. Samples from control and treated, and from resistant and sensitive groups were compared using 1-way ANOVA (analysis of variance). Significantly changed genes obtained from ANOVA were prioritized by a combination of P value and fold change.
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Contributor(s) |
Asiedu M, Wigle D |
Citation(s) |
28862803 |
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Submission date |
Feb 23, 2017 |
Last update date |
Mar 25, 2019 |
Contact name |
Michael K Asiedu |
E-mail(s) |
makasiedu@yahoo.com
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Phone |
5072843482
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Organization name |
Mayo Foundation for Medical Education and Research
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Department |
Surgery
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Street address |
200 Fisrt ST SW
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City |
Rochester |
State/province |
MN |
ZIP/Postal code |
55905 |
Country |
USA |
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Platforms (1) |
GPL570 |
[HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array |
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Samples (58)
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GSM2501480 |
Treated-HSF12,Resistant 1431005375_20 |
GSM2501481 |
Control-HSF20,Sensitive 1431005404_161 |
GSM2501482 |
Control-HSF20,Sensitive 1431005405_162 |
GSM2501483 |
Treated-HSF20,Sensitive 1431005406_163 |
GSM2501484 |
Treated-HSF20,Sensitive 1431005407_164 |
GSM2501485 |
Control-HSF11,Resistant 1431005380_69 |
GSM2501486 |
Control-HSF11,Resistant 1431005381_70 |
GSM2501487 |
Treated-HSF11,Resistant 1431005382_71 |
GSM2501488 |
Treated-HSF11,Resistant 1431005383_72 |
GSM2501489 |
Control-HSF16,Sensitive 1431005384_81 |
GSM2501490 |
Control-HSF16,Sensitive 1431005385_82 |
GSM2501491 |
Treated-HSF16,Sensitive 1431005386_83 |
GSM2501492 |
Treated-HSF16,Sensitive 1431005387_84 |
GSM2501493 |
Control-HSF15,Sensitive 1431005388_93 |
GSM2501494 |
Control-HSF15,Sensitive 1431005389_94 |
GSM2501495 |
Treated-HSF15,Sensitive 1431005390_95 |
GSM2501496 |
Treated-HSF15,Sensitive 1431005391_96 |
GSM2501497 |
Control-HSF7,Resistant 1431005392_117 |
GSM2501498 |
Control-HSF7,Resistant 1431005393_118 |
GSM2501499 |
Treated-HSF7,Resistant 1431005394_119 |
GSM2501500 |
Treated-HSF7,Resistant 1431005395_120 |
GSM2501501 |
Control-HSF8,Resistant 1431005396_121 |
GSM2501502 |
Control-HSF8,Resistant 1431005397_122 |
GSM2501503 |
Treated-HSF8,Resistant 1431005398_123 |
GSM2501504 |
Treated-HSF8,Resistant 1431005399_124 |
GSM2501505 |
Control-HSF14,Sensitive 1431005408_165 |
GSM2501506 |
Control-HSF14,Sensitive 1431005409_166 |
GSM2501507 |
Treated-HSF14,Sensitive 1431005410_167 |
GSM2501508 |
Treated-HSF14,Sensitive 1431005411_168 |
GSM2501509 |
BT20 Treated |
GSM2501510 |
BT20 Control |
GSM2501511 |
H2170 Treated |
GSM2501512 |
H2170 Control |
GSM2501513 |
H520 Treated |
GSM2501514 |
H520 Control |
GSM2501515 |
HCT116 Treated |
GSM2501516 |
HCT116 Control |
GSM2501517 |
HCT15 Treated |
GSM2501518 |
HCT15 Control |
GSM2501519 |
HEPG2 Treated |
GSM2501520 |
HEPG2 Control |
GSM2501521 |
MB157 Treated |
GSM2501522 |
MB157 Control |
GSM2501523 |
MB231 Treated |
GSM2501524 |
MB231 Control |
GSM2501525 |
PANC1 Treated |
GSM2501526 |
PANC1 Control |
GSM2501527 |
SNU Control |
GSM2501528 |
SNU Treated |
GSM2501529 |
HSF 6.1 Control |
GSM2501530 |
HSF 6.1 Treated |
GSM2501531 |
ENDO 6.1 Control |
GSM2501532 |
ENDO 6.1 Treated |
GSM2501533 |
NKX 6.1 Control |
GSM2501534 |
NKX 6.1 Treated |
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Relations |
BioProject |
PRJNA376586 |
Supplementary file |
Size |
Download |
File type/resource |
GSE95298_RAW.tar |
273.4 Mb |
(http)(custom) |
TAR (of CEL) |
GSE95298_Supplementary_file_Metformin_Asiedu_GA_affy_Merged_Technical_Replicates.xls.gz |
19.8 Mb |
(ftp)(http) |
XLS |
Processed data included within Sample table |
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