Background
Methods
Cholesterol pathway genes
Datasets, processing and quality assessment
Abbreviation | Source | Dataset reference | Article reference | Analysis Platform | Samples | PCa | Normal | Unique genes | HP on all samples |
---|---|---|---|---|---|---|---|---|---|
Bertilsson
| Array Express | E-MTAB-1041 | [27] | Microarray, A-MEXP-2087 - Illumina Human HT-12 WG-DASL | 156 | 116 | 40 | 14,149 | Yes |
Chen
| GEO | GSE8218 | Microarray, Affymetrix Human Genome U133A Array | 136 | 65 | 71 | 12,497 | Yes | |
Taylor
| GEO | GSE21034 | [29] | Microarray, Affymetrix Human Exon 1.0 ST Array | 160 | 131 | 29 | 18,294 | No |
TCGA
| TCGA | TCGA | [30] | RNA-Seq, Illumina HiSeq 2000/ Genome Analyzer IIX | 549 | 497 | 52 | 20,504 | No |
Prensner
| dbGaP | phs000443. v1.p1 | [31] | RNA-Seq, Illumina Genome Analyzer | 116 | 78 | 38 | 23,712 | No |
Sboner
| GEO | GSE16560 | [35] | Microarray, Human 6 k Transcriptionally Informative Gene Panel for DASL. | 281 | 281 | 0 | 6102 | No |
Erho
| GEO | GSE46691 | [36] | Exon array, Affymetrix Human Exon 1.0 ST Array [probe set (exon) version] | 545 | 545 | 0 | 17,163 | No |
Stratification of a cohort into balanced and unbalanced datasets
Identification of gene-sets for assessment of stroma content in prostate tissue samples
Gene symbol | Alternative symbol | Gene name | Gene function |
---|---|---|---|
ACAT1 | acetyl-CoA acetyltransferase 1 | Synthesis | |
ACAT2 | acetyl-CoA acetyltransferase 2 | Synthesis | |
HMGCS1 | 3-hydroxy-3-methylglutaryl-CoA synthase 1 | Synthesis | |
HMGCS2 | 3-hydroxy-3-methylglutaryl-CoA synthase 2 | Synthesis | |
HMGCR | 3-hydroxy-3-methylglutaryl-CoA reductase | Synthesis (rate limiting enzyme) | |
MVK | mevalonate kinase | Synthesis | |
PMVK | phosphomevalonate kinase | Synthesis | |
MVD | mevalonate decarboxylase | Synthesis | |
IDI1 | isopentenyl-diphosphate delta isomerase 1 | Synthesis | |
IDI2 | isopentenyl-diphosphate delta isomerase 2 | Synthesis | |
FDPS | farnesyl diphosphate synthase | Synthesis | |
GGPS1 | geranylgeranyl diphosphate synthase 1 | Synthesis | |
FDFT1 | farnesyl-diphosphate farnesyltransferase 1 | Synthesis | |
SQLE | squalene epoxidase | Synthesis | |
LSS | lanosterol synthase | Synthesis | |
DHCR24 | 24-dehydrocholesterol reductase | Synthesis | |
CYP51A1 | cytochrome P450 family 51 subfamily A polypeptide 1 | Synthesis | |
TM7SF2 | transmembrane 7 superfamily member 2 | Synthesis | |
FAXDC2 | C5orf4 | fatty acid hydroxylase domain containing 2 | Synthesis |
MSMO1 | SC4MOL | methylsterol monooxygenase | Synthesis |
NSDHL | NAD(P) dependent steroid dehydrogenase-like | Synthesis | |
HSD17B7 | hydroxysteroid (17-beta) dehydrogenase 7 | Synthesis | |
EBP | emopamil binding protein (sterol isomerase) | Synthesis | |
SC5D | SC5DL | sterol-C5-desaturase | Synthesis |
DHCR7 | 7-dehydrocholesterol reductase | Synthesis (last step before cholesterol) | |
CEL | carboxyl ester lipase | Esterification | |
LIPA | lipase A, lysosomal acid, cholesterol esterase | Esterification | |
SOAT1 | sterol O-acetyltransferase 1 | Esterification | |
SOAT2 | sterol O-acetyltransferase 2 | Esterification | |
ABCA1 | ATP-binding cassette, sub-family A | Efflux | |
ABCG1 | ATP-binding cassette, sub-family G | Efflux | |
SLCO2B1 | solute carrier organic anion transporter family member 2B1 | Transport | |
SLCO1B3 | solute carrier organic anion transporter family member 1B3 | Transport | |
LDLR | low density lipoprotein receptor | Uptake | |
APOE | apolipoprotein E | Component for IDL, HDL and VLDL | |
SREBF1 | sterol binding element transcription factor 1 | Transcriptional activation | |
SREBF2 | sterol binding element transcription factor 2 | Transcriptional activation (main activator) | |
SCAP | SREBF chaperone | Transcriptional activation | |
MBTPS1 | S1P | membrane bound transcription factor peptidase site 1 | Transcriptional activation |
MBTPS2 | S2P | membrane bound transcription factor peptidase site 2 | Transcriptional activation |
INSIG1 | insulin induced gene 1 | HMGCR degradation | |
INSIG2 | insulin induced gene 2 | HMGCR degradation | |
AMFR | GP78 | autocrine motility factor receptor E3 ubiquitin protein ligase | HMGCR degradation |
NR1H3 | LXRA | nuclear receptor subfamily 1 group H member 3 | Transcriptional repression |
NR1H2 | LXRB | nuclear receptor subfamily 1 group H member 2 | Transcriptional repression |
RXRA | retinoid X receptor alpha | Transcriptional repression | |
RXRB | retinoid X receptor beta | Transcriptional repression | |
MYLIP | IDOL | myosin regulatory light chain interacting protein | Degradation of LDLR |
Validation of stroma gene-sets in the histopathology cohorts
Defining balanced and unbalanced data-sets in cohorts lacking histopathology
Rank based meta-analysis for combined cohorts
Gene ontology analysis
Results
Differentially expressed genes in seven publicly available prostate cancer cohorts controlled for stroma tissue confounding
Robust stroma assessment using gene set enrichment analysis (GSEA) with sets of stroma-enriched genes
Balancing the stroma content in cohorts with missing histopathology
Transcriptional downregulation of genes in the cholesterol synthesis pathway when adjusting for stroma tissue confounding
GO term | q-value using Bertilsson gene- set | q-value using Chen gene-set |
---|---|---|
Cell Adhesion | 6.7e-8 | 6.6e-8 |
Signal | 1.3e-7 | 1.6e-8 |
Glycoprotein | 2.0e-8 | 1.1e-7 |
Steroid Biosynthesis | 5.4e-6 | 4.3e-6 |
Cholesterol Biosynthesis | 3.7e-4 | 1.7e-5 |