Background
Methods
Tissue samples and clinical data
Characteristic | Non-metastatic patients (n = 45) | Liver metastatic patients (n = 46) |
---|---|---|
Mean age, years | 60.96 ± 14.4 | 63.17 ± 10.21 |
Mean primary tumor thickness (mm) | 10.13 ± 2.97 | 11.45 ± 2.76 |
Mean tumor largest diameter (mm) | 14.64 ± 4.14 | 15.08 ± 4.01 |
Gender, No. of patients | ||
Male | 27 | 29 |
Female | 18 | 17 |
Location of tumor | ||
Anterior | 3 | 4 |
On equator | 29 | 27 |
Posterior | 6 | 13 |
All | 0 | 1 |
NA | 7 | 1 |
Histopathologic cell type | ||
Epithelioid | 9 | 18 |
Spindle | 8 | 18 |
Mixed | 16 | 9 |
NA | 12 | 1 |
Extrascleral extension | ||
No | 31 | 31 |
Yes | 10 | 9 |
NA | 4 | 6 |
Chr 3 | ||
Monosomy | 17 | 31 |
Disomy | 24 | 6 |
Partial monosomy | 2 | 3 |
NA | 2 | 6 |
Significant differential gene analysis
Gene ontology (GO) analysis
Pathway analysis
Signal-net analysis
Data analysis
Results
Clinical characteristics of the two group samples
Liver metastases-related differential expression genes
Gene symbol | P value | Mean of intensities: no metastasis | Mean of intensities: metastasis | Fold change |
---|---|---|---|---|
NEURL1B | 1.67 × 10-9
| 51.47 | 88.42 | 1.72 |
EXT1 | 2.82 × 10-9
| 203.15 | 362.35 | 1.78 |
DERL1 | 4.89 × 10-9
| 178.31 | 412.54 | 2.31 |
GALNTL4 | 1.22 × 10-8
| 57.44 | 128.49 | 2.24 |
MR1 | 1.41 × 10-8
| 60.08 | 98.74 | 1.64 |
DDX39 | 3.31 × 10-8
| 347.31 | 556.46 | 1.60 |
HTR2B | 3.49 × 10-8
| 41.04 | 574.49 | 14.00 |
RAB2A | 5.29 × 10-8
| 363.13 | 741.99 | 2.04 |
C10orf26 | 6.68 × 10-8
| 376.40 | 569.30 | 1.51 |
GJC1 | 7.39 × 10-8
| 25.95 | 75.05 | 2.89 |
CHL1 | 8.99 × 10-8
| 80.84 | 17.12 | 0.21 |
ZNF33B | 2.17 × 10-8
| 41.91 | 21.24 | 0.51 |
OVOS2 | 2.44 × 10-8
| 857.96 | 185.87 | 0.22 |
EIF1B | 3.35 × 10-7
| 1008.84 | 567.87 | 0.56 |
PHLDA1 | 5.22 × 10-7
| 370.24 | 134.93 | 0.36 |
PLSCR4 | 5.34 × 10-7
| 114.83 | 53.41 | 0.47 |
MEGF10 | 8.38 × 10-7
| 165.39 | 26.05 | 0.16 |
ZNF415 | 1.19 × 10-6
| 37.03 | 13.91 | 0.38 |
ZNF667 | 1.25 × 10-6
| 34.08 | 16.02 | 0.47 |
MEGF10 | 1.66 × 10-6
| 22.24 | 10.21 | 0.46 |
Gene symbol | P value | Mean of intensities: no metastasis | Mean of intensities: metastasis | Fold change |
---|---|---|---|---|
HTR2B | 3.49 × 10-8
| 5.36 | 9.17 | 14.00 |
PPM1K | 2.96 × 10-6
| 7.67 | 9.39 | 3.30 |
SSX4 | 1.03 × 10-4
| 5.65 | 7.28 | 3.09 |
PTGER4 | 3.01 × 10-3
| 6.75 | 8.36 | 3.06 |
MEGF10 | 8.38 × 10-7
| 7.37 | 4.70 | 0.16 |
SYNPR | 1.25 × 10-5
| 9.15 | 6.83 | 0.20 |
CHL1 | 8.99 × 10-8
| 6.34 | 4.10 | 0.21 |
OVOS2 | 2.44 × 10-7
| 9.74 | 7.54 | 0.22 |
LOC100128252 | 5.70 × 10-6
| 7.54 | 5.55 | 0.25 |
MPPED2 | 5.58 × 10-6
| 6.28 | 4.40 | 0.27 |
CNTN3 | 1.37 × 10-5
| 5.40 | 3.60 | 0.29 |
PCDH20 | 2.94 × 10-3
| 5.82 | 4.07 | 0.30 |
Significant GOs
GO item | Fold enrichment | P value |
---|---|---|
Germ cell programmed cell death | 32.29 | 2.80 × 10-3
|
Developmental programmed cell death | 19.37 | 8.95 × 10-3
|
Protein retention in ER lumen | 13.84 | 1.80 × 10-2
|
Germ cell migration | 13.45 | 3.65 × 10-4
|
Melanocyte differentiation | 9.22 | 8.27 × 10-3
|
Mitotic cell cycle spindle assembly checkpoint | 8.81 | 4.36 × 10-2
|
Negative regulation of mitotic metaphase/anaphase transition | 8.81 | 4.36 × 10-2
|
Pigmentation during development | 8.69 | 1.14 × 10-4
|
Pigment cell differentiation | 8.61 | 1.01 × 10-2
|
Antigen processing and presentation of peptide antigen via MHC class I | 7.60 | 1.44 × 10-2
|
Positive regulation of calcium ion transport into cytosol | 6.46 | 2.26 × 10-2
|
Regulation of calcium ion transport into cytosol | 5.57 | 1.16 × 10-2
|
T cell proliferation | 4.78 | 4.95 × 10-2
|
Regulation of transforming growth factor beta receptor signaling pathway | 4.14 | 3.15 × 10-2
|
Positive regulation of homeostatic process | 4.04 | 3.42 × 10-2
|
Response to vitamin A | 3.84 | 4.00 × 10-2
|
Pigmentation | 3.83 | 9.50 × 10-3
|
Mitotic cell cycle checkpoint | 3.75 | 4.30 × 10-2
|
Regulation of calcium ion transport | 3.74 | 5.31 × 10-3
|
Extracellular matrix organization | 3.73 | 3.63 × 10-4
|
Alcohol biosynthetic process | 3.67 | 4.62 × 10-2
|
Regulation of metal ion transport | 3.59 | 3.49 × 10-3
|
Leukocyte mediated immunity | 3.38 | 5.04 × 10-3
|
Cellular response to insulin stimulus | 3.32 | 1.83 × 10-2
|
Regulation of ion transport | 3.26 | 3.51 × 10-3
|
Lymphocyte mediated immunity | 3.23 | 2.09 × 10-2
|
Response to organic cyclic substance | 3.20 | 1.30 × 10-3
|
Response to toxin | 3.18 | 3.98 × 10-2
|
Double-strand break repair | 3.12 | 4.23 × 10-2
|
Sphingolipid metabolic process | 3.01 | 2.82 × 10-2
|
Response to molecule of bacterial origin | 3.00 | 1.70 × 10-2
|
Adaptive immune response | 2.94 | 3.16 × 10-2
|
Response to lipopolysaccharide | 2.94 | 3.16 × 10-2
|
Adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains | 2.94 | 3.16 × 10-2
|
Cellular response to hormone stimulus | 2.91 | 2.77 × 10-3
|
Response to insulin stimulus | 2.91 | 1.22 × 10-2
|
Membrane lipid metabolic process | 2.79 | 3.91 × 10-2
|
Activation of MAPK activity | 2.76 | 4.11 × 10-2
|
Immune effector process | 2.65 | 8.66 × 10-3
|
Protein processing | 2.59 | 2.27 × 10-2
|
Extracellular structure organization | 2.57 | 4.72 × 10-3
|
Response to oxidative stress | 2.56 | 4.95 × 10-3
|
Positive regulation of MAP kinase activity | 2.53 | 3.86 × 10-2
|
Regulation of MAP kinase activity | 2.52 | 1.21 × 102 |
Amine transport | 2.46 | 2.99 × 10-2
|
Camera-type eye development | 2.41 | 4.79 × 10-2
|
Carbohydrate biosynthetic process | 2.41 | 4.79 × 10-2
|
Protein oligomerization | 2.41 | 7.85 × 10-3
|
Protein maturation | 2.38 | 3.54 × 10-2
|
Nucleotide biosynthetic process | 2.26 | 1.29 × 102 |
Nucleobase, nucleoside and nucleotide biosynthetic process | 2.17 | 1.69 × 10-2
|
Nucleobase, nucleoside, nucleotide and nucleic acid biosynthetic process | 2.17 | 1.69 × 10-2
|
Cell proliferation | 2.15 | 2.12 × 10-4
|
Muscle organ development | 2.14 | 1.41 × 102 |
Regulation of neurogenesis | 2.14 | 3.34 × 10-2
|
Skeletal system development | 2.13 | 2.21 × 10-3
|
Response to peptide hormone stimulus | 2.10 | 4.96 × 10-2
|
Transmembrane receptor protein tyrosine kinase signaling pathway | 2.02 | 2.20 × 10-2
|
Regulation of nervous system development | 2.02 | 3.63 × 10-2
|
Nitrogen compound biosynthetic process | 1.99 | 5.98 × 10-3
|
Enzyme linked receptor protein signaling pathway | 1.98 | 4.86 × 10-3
|
Response to drug | 1.94 | 3.62 × 10-2
|
Blood vessel development | 1.84 | 4.11 × 10-2
|
Response to DNA damage stimulus | 1.82 | 1.20 × 10-2
|
Induction of apoptosis | 1.82 | 2.14 × 10-2
|
Induction of programmed cell death | 1.81 | 2.19 × 10-2
|
Positive regulation of apoptosis | 1.80 | 7.74 × 10-3
|
Vasculature development | 1.80 | 4.83 × 10-2
|
Positive regulation of programmed cell death | 1.79 | 8.09 × 10-3
|
Positive regulation of cell death | 1.78 | 8.74 × 10-3
|
M phase | 1.77 | 2.70 × 10-2
|
Response to hormone stimulus | 1.76 | 1.98 × 10-2
|
Response to endogenous stimulus | 1.75 | 1.46 × 10-2
|
Cell cycle phase | 1.72 | 1.82 × 10-2
|
Response to abiotic stimulus | 1.67 | 3.73 × 10-2
|
Protein kinase cascade | 1.66 | 3.89 × 10-2
|
Cellular response to stress | 1.65 | 9.67 × 10-3
|
Response to organic substance | 1.61 | 5.45 × 10-3
|
Phosphorylation | 1.57 | 5.41 × 10-3
|
Oxidation reduction | 1.57 | 1.51 × 10-2
|
Phosphate metabolic process | 1.56 | 2.49 × 10-3
|
Phosphorus metabolic process | 1.56 | 2.49 × 10-3
|
Cell cycle process | 1.54 | 2.79 × 10-2
|
Protein amino acid phosphorylation | 1.50 | 2.49 × 10-2
|
Immune response | 1.50 | 2.35 × 10-2
|
Regulation of cell proliferation | 1.44 | 3.02 × 10-2
|
Regulation of programmed cell death | 1.43 | 2.88 × 10-2
|
Regulation of cell death | 1.43 | 3.01 × 10-2
|
Regulation of apoptosis | 1.41 | 3.91 × 10-2
|
GO item | Fold enrichment | P value |
---|---|---|
Calcium-dependent cell-cell adhesion | 9.49 | 3.90 × 10-2
|
Response to acid | 9.09 | 4.22 × 10-2
|
Embryonic skeletal system development | 5.67 | 4.04 × 10-3
|
Response to vitamin | 5.51 | 1.26 × 10-2
|
Regulation of cell shape | 5.39 | 3.75 × 10-2
|
Regulation of Rho protein signal transduction | 5.14 | 2.36 × 10-3
|
Pigmentation | 4.93 | 4.68 × 10-2
|
Cartilage development | 4.91 | 1.85 × 10-2
|
Skeletal system morphogenesis | 3.90 | 1.88 × 10-2
|
Regulation of cell morphogenesis | 3.89 | 9.22 × 10-3
|
Translational elongation | 3.60 | 4.97 × 10-2
|
Muscle tissue development | 3.49 | 2.85 × 10-2
|
Homophilic cell adhesion | 3.33 | 3.40 × 10-2
|
Regulation of neuron differentiation | 3.28 | 3.59 × 10-2
|
Embryonic organ morphogenesis | 3.28 | 3.59 × 10-2
|
Regulation of cell development | 3.19 | 7.23 × 10-3
|
Regulation of Ras protein signal transduction | 3.12 | 8.25 × 10-3
|
Muscle organ development | 3.10 | 8.54 × 10-3
|
Regulation of neurogenesis | 3.07 | 2.66 × 10-2
|
Response to drug | 3.03 | 9.75 × 10-3
|
Embryonic organ development | 2.96 | 3.09 × 10-2
|
Regulation of small GTPase mediated signal transduction | 2.89 | 7.88 × 10-3
|
Skeletal system development | 2.74 | 4.38 × 10-3
|
Heart development | 2.71 | 2.85 × 10-2
|
Regulation of nervous system development | 2.65 | 4.85 × 10-2
|
Cell-cell adhesion | 2.64 | 1.37 × 10-2
|
Negative regulation of cell proliferation | 2.62 | 4.07 × 10-3
|
Cell adhesion | 2.60 | 2.99 × 10-5
|
Biological adhesion | 2.59 | 3.06 × 10-5
|
Actin cytoskeleton organization | 2.57 | 3.59 × 10-2
|
Actin filament-based process | 2.41 | 4.79 × 10-2
|
Chordate embryonic development | 2.20 | 3.87 × 10-2
|
Embryonic development ending in birth or egg hatching | 2.18 | 4.03 × 10-2
|
Cytoskeleton organization | 2.17 | 1.68 × 10-2
|
Regulation of cell proliferation | 2.03 | 2.54 × 10-3
|
Response to organic substance | 1.71 | 3.85 × 10-2
|