Background
Methods
Patients
Primary tumour
|
Liver metastases
|
Clinical outcome
| |||||
---|---|---|---|---|---|---|---|
No.
|
Type
|
Treatment
|
Tumour burden
|
Largest diameter
|
Response
|
Status
|
Laboratory characterisation of exosomes
|
1 | Choroidal | I-125 | 10-24% | 15 mm | PR | Alive 29 mo | RNA, FACS, PCR |
2 | Choroidal | En | 25-50% | 25 mm | PR | Dead 25 mo | RNA |
3 | Choroidal | I-125 + En | 10-24% | 45 mm | PR | Dead 17 mo | RNA |
4 | Choroidal | En | <10% | 20 mm | PR | Alive 17 mo | EM |
5 | Choroidal | En | <10% | 55 mm | PR | Dead 14 mo | EC, RNA, PCR |
6 | Choroidal | En | 10-24% | 35 mm | PR | Alive 13 mo | EC, RNA, FACS |
7 | Choroidal | I-125 | <10% | 23 mm | SD | Alive 13 mo | EC, RNA, PCR |
8 | Choroidal | Ru-106 | 25-50% | 100 mm | PD | Alive 11 mo | EC, RNA, PCR, FACS |
9 | Choroidal | En | <10% | 40 mm | PR | Alive 10 mo | EC, RNA, PCR |
10 | Choroidal | Ru-106 + En | <10% | 30 mm | SD | Alive 7 mo | EC |
11 | Choroidal | En | <10% | 15 mm | SD | Alive 6 mo | EC |
12 | Choroidal | En | 10-24% | 25 mm | PR | Alive 5 mo | EC |
Isolated liver perfusion
Sample collection and exosome isolation
Cell culture and exosome isolation
Flow cytometry analysis
Electron microscopy
Western blot
Total RNA analysis
MicroRNA analysis
Statistical analysis
Results
Clinical characteristics
Liver perfusates contains exosomes
Patients have more circulating exosomes compared to healthy controls
RNA profiles and miRNA analyses of liver perfusate exosomes
KEGG pathway | P value | Number of genes | Genes |
---|---|---|---|
Hedgehog signalling | 0.009 | 14 | BMP2, BMP6, BTRC, CSNK1A1, CSNK1E, CSNK1G3, GLI3, IHH, LRP2, RAB23, SMO, SUFU, WNT16, WNT3A |
Glioma | 0.010 | 11 | AKT3, CDK4, CDK6, E2F3, IGF1, IGF1R, MAPK1, PIK3CA, PIK3R1, PTEN, SOS2 |
Melanoma | 0.010 | 15 | AKT3, CDK4, CDK6, E2F3, FGF19, FGF2, FGF7, IGF1, IGF1R, MAPK1, PDGFC, PDGFD, PIK3CA, PIK3R1, PTEN |
Prostate cancer | 0.010 | 18 | AKT3, CCNE1, CREB3, CREB3L2, CREB5, CTNNB1, E2F3, FOXO1A, IGF1, IGF1R, LEF1, MAPK1, PDGFC, PDGFD, PIK3CA, PIK3R1, PTEN, SOS2 |
Focal adhesion | 0.014 | 30 | AC128683.3, AKT3, ARHGAP5, COL4A1, CRKL, CTNNB1, IGF1, IGF1R, ITGA1, ITGA2, ITGA4, ITGB8, LAMC1, MAPK1, MAPK8, MYL12A, PDGFC, PDGFD, PIK3CA, PIK3R1, PPP1R12A, PTEN, RAC1, RAP1A, RAPGEF1, SOS2, VAV3, VCL, XIAP, ZYX |
Pathways in cancer | 0.014 | 43 | AKT3, ARNT, AXIN2, BMP2, CBL, CCNE1, CDK4, CDK6, COL4A1, CRKL, CTNNB1, DVL1, E2F3, EVI1, FGF19, FGF2, FGF7, FOXO1A, GLI3, IGF1, IGF1R, ITGA2, KITLG, LAMC1, LEF1, MAPK1, MAPK8, PIK3CA, PIK3R1, PTEN, RAC1, RASSF5, RET, RUNX1T1, SMO, SOS2, STK4, SUFU, TPM3, VHL, WNT16, WNT3A, XIAP |
Circadian rhythm - mammal | 0.015 | 6 | ASH1L, EHHADH, MLL5, SETD1B, SUV420H1, WHSC1 |
mTOR signalling | 0.017 | 12 | AC026713.5, AKT3, CAB39, EIF4B, IGF1, MAPK1, PIK3CA, PIK3R1, PRKAA2, RPS6KA3, TSC1, ULK1 |
Adipocytokine signalling | 0.038 | 10 | ADIPOR1, AKT3, JAK2, LEPR, MAPK8, PPARGC1A, PRKAA2, PRKAB2, PRKAG2, PRKAG3 |
Lysine degradation | 0.040 | 6 | ASH1L, EHHADH, MLL5, SETD1B, SUV420H1, WHSC1 |
Insulin signalling | 0.041 | 21 | AKT3, CBL, CRKL, FASN, FOXO1A, INSR, MAPK1, MAPK8, PDE3B, PHKA1, PIK3CA, PIK3R1, PPARGC1A, PRKAA2, PRKAB2, PRKAG2, PRKAG3, RAPGEF1, SKIP, SOS2, TSC1 |
Endometrial cancer | 0.049 | 9 | AKT3, AXIN2, CTNNB1, LEF1, MAPK1, PIK3CA, PIK3R1, PTEN, SOS2 |
Cytokine-cytokine receptor interaction | 0.049 | 18 | ACVR2A, ACVR2B, BMP2, BMPR1A, BMPR2, CCL21, CCR7, CCR8, CXCR5, IL1RAP, IL23R, IL4R, IL6ST, IL9R, KITLG, LEPR, LIFR, PDGFC |