Background
Methods
Osteosarcoma tissues and clinical information
N | Disease free survival | Overall survival | ||||||||
---|---|---|---|---|---|---|---|---|---|---|
P | HR | 95.0% CI | P | HR | 95.0% CI | |||||
L | U | L | U | |||||||
Sex | Male | 29 | 0.86 | 0.07* | ||||||
Female | 29 | 0.86 | 1.11 | 0.36 | 3.44 | 0.08 | 3.49 | 0.86 | 14.28 | |
Age group | <=15 y | 14 | 0.76 | 0.79 | ||||||
15-20 y | 23 | 0.94 | 1.10E + 04 | 0 | 1.40E + 116 | 0.5 | 1.82 | 0.32 | 10.42 | |
21-30 y | 11 | 0.94 | 3.70E + 04 | 0 | 4.40E + 116 | 0.72 | 0.73 | 0.13 | 4.05 | |
31-40 y | 1 | 0.93 | 5.30E + 04 | 0 | 6.40E + 116 | 0.97 | 0 | 0 | 1.90E + 282 | |
>40 y | 9 | 1 | 1.02 | 0 | 3.90E + 225 | 0.99 | 0 | 0 | ||
Tumor location | limbs | 51 | 0.28 | 0.97 | ||||||
Others | 7 | 0.48 | 23.34 | 0.004 | 1.60E + 05 | 0.97 | 0.97 | 0.12 | 7.72 | |
Enneking stage | I | 4 | 0.96 | 0.43 | ||||||
IIA | 19 | 0.78 | 0.71 | 0.06 | 7.88 | 0.17 | 0.1 | 0.004 | 2.74 | |
IIB | 2 | 0.631 | 0.59 | 0.07 | 5.01 | 0.1 | 0.09 | 0.01 | 1.61 | |
III | 1 | 0.897 | 0.83 | 0.05 | 13.39 | 0.99 | 0 | 0 | ||
Neoadjuvant chemotherapy | No | 10 | 0.51 | 1.5E-4* | ||||||
Yes | 30 | 0.51 | 1.51 | 0.44 | 5.15 | 0.003 | 11.85 | 2.36 | 59.45 | |
Adjuvant chemotherapy | No | 3 | 0.21 | 0.41 | ||||||
Yes | 19 | 0.43 | 0.04 | 0 | 129.34 | 0.61 | 0.04 | 0 | 1.20E + 04 | |
Recurrence | No | 50 | 0.49 | |||||||
Yes | 8 | 0.49 | 2.05 | 0.26 | 16.26 | |||||
Metastasis | No | 38 | 0.045* | |||||||
Yes | 11 | 0.436 | 0.01 | 0 | 2.40E + 03 |
Array comparative genomic hybridization and pathway enrichment analysis
RNA-seq analysis
Immunohistochemical analysis of WNT1, β-catenin, c-myc, and cyclin D1 expression
Statistics
Results
Several signaling pathways are genetically altered in osteosarcoma
KEEG pathways | P-value | Gene name cohort |
---|---|---|
VEGF signaling pathway | 0.000611811 |
MAPK14, AKT1, PLA2G2D, PLA2G2E, NFATC4, PIK3CD, PLA2G2A, PLA2G5, MAPK1, MAPK13, PTK2, RAC1, RAC3, PLA2G2F, VEGFA, CASP9, PIK3R3, SPHK1, SH2D2A, CDC42P2, CDC42
|
mTOR signaling pathway | 0.024894273 |
AKT1, MTOR, RICTOR, PIK3CD, PRKAA1, PRKAA2, MAPK1, RPTOR, RPS6KA1, VEGFA, PIK3R3, ULK2
|
Tight junction | 0.044332801 |
INADL, EXOC3, CSNK2B, CLDN19, AKT1, CLDN14, CLDN17, LLGL2, LLGL1, MYH6, MYH7, F11R, ASH1L, PRKCZ, CGN, JAM2, RAB3B, RAB13, ACTB, ACTG1, CLDN5, CLDN8, CRB3, TJAP1, CDC42P2, CDC42
|
Synthesis and degradation of ketone bodies | 0.019871373 |
HMGCL, HMGCS1, HMGCS2, OXCT1
|
C21-Steroid hormone metabolism | 0.04221587 |
CYP11B1, CYP11B2, HSD3B1, HSD3B2
|
Peptidoglycan biosynthesis | 0.017208179 |
PGLYRP2, PGLYRP3, PGLYRP4
|
Ether lipid metabolism | 0.006547877 |
AGPAT1, PLA2G2D, PLA2G2E, PAFAH2, ENPP2, PLA2G2A, PLA2G5, AGPAT3, PLA2G2F, PPAP2B
|
Arachidonic acid metabolism | 0.02227667 |
CYP2J2, CYP4A11, GPX6, PLA2G2D, GPX5, GPX7, PLA2G2E, CYP4F3, PLA2G2A, PLA2G5, PLA2G2F, CYP4F2, CBR3
|
Alpha-Linolenic acid metabolism | 0.003362937 |
PLA2G2D, PLA2G2E, ACOX1, PLA2G2A, PLA2G5, PLA2G2F, FADS2
|
Nitrogen metabolism | 0.007842327 |
CTH, CA14, CA1, CA2, CA3, CA6, CA8, ASRGL1
|
Glycan structures-biosynthesis 2 | 0.025972282 |
PIGK, B3GALT5, ST6GALNAC3, PIGP, PIGV, ST3GAL1, ST3GAL3, ST6GALNAC5, B4GALT3, B4GALT2, B3GALT4, GPAA1, PIGM, PIGL
|
Biosynthesis of unsaturated fatty acids | 0.021314211 |
ACOT7, FASN, ACOT11, FADS1, ACOX1, FADS2, TECR
|
Antigen processing and presentation | 0.028228218 |
CTSS, HLA-DMA, HLA-DMB, HLA-DOA, HLA-DOB, HLA-DPA1, HLA-DQA2, HLA-DRB5, HLA-F, HSPA1B, HSPA1A, HSPA1L, HSP90AB1, NFYA, NFYC, RFX5, TAP1, TAP2, CALR
|
Fc epsilon RI signaling pathway | 0.000481297 |
MAPK14, AKT1, FCER1A, FCER1G, PLA2G2D, GRB2, PLA2G2E, LYN, PIK3CD, PLA2G2A, PLA2G5, MAPK1, MAPK13, MAP2K3, MAP2K7, RAC1, RAC3, PLA2G2F, TNF, VAV1, PIK3R3
|
Insulin signaling pathway | 0.047775005 |
FLOT1, CRKL, AKT1, FASN, EXOC7, MTOR, GRB2, INSR, PFKL, PIK3CD, PKLR, PRKAA1, PRKAA2, PRKAB2, PRKACA, PRKACB, PRKCZ, MAPK1, RPTOR, PTPRF, SHC1, SREBF1, PIK3R3, MKNK1, TRIP10
|
GnRH signaling pathway | 0.04873803 |
ADCY8, MAPK14, ADCY4, PLA2G2D, GRB2, PLA2G2E, ITPR3, JUN, PLA2G2A, PLA2G5, PRKACA, PRKACB, MAPK1, MAPK7, MAPK13, MAP2K3, MAP2K7, PLA2G2F, CDC42P2, CDC42
|
Alzheimer’s disease | 0.020850782 |
NCSTN, BACE2, APP, APH1A, C1QA, TNF, C1QB, C1QC
|
Asthma | 0.003038215 |
FCER1A, FCER1G, HLA-DMA, HLA-DMB, HLA-DOA, HLA-DOB, HLA-DPA1, HLA-DQA2, HLA-DRB5, TNF
|
Systemic lupus erythematosus | 2.49E-06 |
FCGR1A, FCGR2A, FCGR2B, FCGR3A, HIST1H2AB, HIST1H2AE, HIST1H2BD, H3F3B, H3F3A, HLA-DMA, HLA-DMB, HLA-DOA, HLA-DOB, HLA-DPA1, HLA-DQA2, HLA-DRB5, HIST2H2AB, C1QA, TNF, C1QB, C1QC, C2, C3, C6, C7, C8A, C8B, C9, HIST1H2AG, SMCHD1, HIST1H2AI, HIST1H2AK, HIST1H2AL, HIST1H2AM, HIST1H2AJ, HIST1H2AC, HIST2H2AC, HIST1H2BC, HIST1H2BE, HIST1H2BF, HIST1H2BG, HIST1H2BI, HIST1H2BO, HIST2H2BE, HIST1H3A, HIST1H3B, HIST1H3C, HIST1H3D, HIST1H3E, HIST1H3F, HIST1H3G, HIST1H3H, HIST1H3I, HIST1H3J, HIST4H4, HIST1H4A, HIST1H4B, HIST1H4C, HIST1H4D, HIST1H4E, HIST1H4F, HIST1H4H, HIST1H4I, HIST1H4J, HIST1H4K, HIST1H4L, HIST2H4A, HIST2H4B, HIST1H4G, HIST1H2AH, HIST1H2BK, HIST1H2BJ
|
Allograft rejection | 0.046891168 |
HLA-DMA, HLA-DMB, HLA-DOA, HLA-DOB, HLA-DPA1, HLA-DQA2, HLA-DRB5, HLA-F, TNF
|
KEEG pathways | P value | Gene name cohort |
---|---|---|
Wnt signaling pathway | 0.01039 |
FRAT1, CSNK1A1L, CTBP2, PRICKLE2, FRAT2, GSK3B, PLCB2, SFRP5, MAP3K7, TCF7L2, WNT5A, WNT6, WNT8B, FZD5, WNT10A, FZD7, FZD8, BTRC
|
Hedgehog signaling pathway | 0.012811 |
CSNK1A1L, STK36, GSK3B, SUFU, WNT5A, WNT6, WNT8B, WNT10A, BTRC
|
Adherens junction | 0.014329 |
SORBS1, WASF3, FER, FYN, PVRL3, MLLT4, PARD3, MAP3K7, TCF7L2, VCL, WASF1
|
Metabolism of xenobiotics by cytochrome P450 | 0.006437 |
AKR1C4, GSTO2, CYP2C19, CYP2C8, CYP2C9, CYP2C18, AKR1C1, AKR1C2, UGT1A8, AKR1C3, GSTO1
|
PPAR signaling pathway | 0.039963 |
SORBS1, CYP27A1, FABP7, ACSL3, ACADL, ME1, ACSL5, SCD, ACOX2
|
Non-homologous end-joining | 0.001607 |
DNTT, POLL, DCLRE1C, XRCC5, NHEJ1
|
Phosphatidylinositol signaling system | 0.040426 |
DGKH, INPP5D, PLCE1, CALML5, PIK3R1, GNG7, PIP4K2A, PLCB2, PTEN, PLCD4, DGKD
|
ECM-receptor interaction | 0.032505 |
COL6A3, FNDC3A, SV2C, FN1, ITGA1, ITGB1, LAMA4, THBS1, THBS2, ITGA8, CD47
|
T cell receptor signaling pathway | 0.020903 |
RASGRP1, CHUK, MAP3K8, CTLA4, FYN, ICOS, NFKB2, PIK3R1, PRKCQ, PAK6, CBLB, CD28
|
Melanogenesis | 0.007761 |
ADCY5, CREB1, GSK3B, MITF, CALML5, PLCB2, TCF7L2, WNT5A, WNT6, WNT8B, FZD5, WNT10A, FZD7, FZD8
|
Basal cell carcinoma | 0.00088 |
STK36, GSK3B, SUFU, TCF7L2, WNT5A, WNT6, WNT8B, FZD5, WNT10A, FZD7, FZD8
|