Background
Methods
Selection of clinical LUSC tissue samples
Clinicopathological parameters |
n
| Relevant expression of HOXA11 (2-ΔCq) | |||
---|---|---|---|---|---|
Mean ± SD |
t
| P value | |||
Tissue | Adjacent non-cancerous lung tissue | 23 | 0.347 ± 0.304 | − 1.501a | 0.138 |
LUSC | 23 | 0.764 ± 1.288 | |||
Age (years) | < 60 | 15 | 0.892 ± 1.555 | 0.647a | 0.525 |
≥ 60 | 8 | 0.523 ± 0.529 | |||
Gender | Male | 18 | 0.850 ± 1.445 | 0.597a | 0.557 |
Female | 5 | 0.455 ± 0.315 | |||
Smoke | No | 12 | 0.354 ± 0.255 | − 1.655a | 0.113 |
Yes | 11 | 1.211 ± 1.777 | |||
Tumor size (cm) | ≤ 3 | 7 | 1.401 ± 2.219 | 1.084a | 0.319 |
> 3 | 16 | 0.485 ± 0.438 | |||
EGFR amplification | No | 17 | 0.547 ± 0.477 | − 0.829a | 0.444 |
Yes | 6 | 1.379 ± 2.441 | |||
EGFR protein | High | 5 | 0.638 ± 0.613 | 0.242a | 0.811 |
Low | 18 | 0.799 ± 1.433 | |||
TNM | I–II | 10 | 0.250 ± 0.188 | − 1.756a | 0.094 |
III–IV | 13 | 1.159 ± 1.621 | |||
Vascular invasion | Yes | 3 | 0.768 ± 0.535 | − 0.006 a | 0.995 |
No | 20 | 0.763 ± 1.375 | |||
Pathological grading | I | 0 | F = 0.574b | 0.457 | |
II | 16 | 0.900 ± 1.524 | |||
III | 7 | 0.344 ± 0.130 |
Total RNA isolation
qRT-PCR assay
Data mining and analyzing
Screening co-expressed genes of HOXA11
Enrichment analysis and pathway annotation
Statistical analysis
Results
HOXA11 expression and clinicopathological features in LUSC using qRT-PCR
Verification of HOXA11 expression in TCGA and Oncomine
Clinicopathological parameters |
n
| Relevant expression of HOXA11 (2-ΔCq) | |||
---|---|---|---|---|---|
Mean ± SD |
t
| P value | |||
Tissue | Adjacent non-cancerous lung tissue | 18 | 1.209 ± 0.813 | − 20.240a | 1.5855E−17 |
Cancer | 475 | 5.531 ± 2.054 | |||
Age (years) | < 60 | 41 | 5.578 ± 2.374 | 0.087a | 0.931 |
≥ 60 | 199 | 5.609 ± 2.080 | |||
Gender | Male | 353 | 5.593 ± 2.049 | 1.123a | 0.262 |
Female | 120 | 5.349 ± 2.065 | |||
Status | Dead | 204 | 5.445 ± 2.003 | − 0.799a | 0.425 |
Alive | 269 | 5.597 ± 2.093 | |||
Neoplasm cancer status | With tumor | 108 | 5.335 ± 2.211 | − 1.086a | 0.278 |
Tumor-free | 299 | 5.590 ± 2.037 | |||
M | M0 | 390 | 5.549 ± 2.069 | F = 0.224b | 0.800 |
M1 | 4 | 6.041 ± 2.528 | |||
MX | 73 | 5.431 ± 1.974 | |||
T | T1–T2 | 385 | 5.526 ± 2.029 | − 0.119a | 0.906 |
T3–T4 | 88 | 5.555 ± 2.172 | |||
N | N0–N1 | 424 | 5.525 ± 2.050 | F = 2.565b | 0.078 |
N2–N3 | 45 | 5.780 ± 1.974 | |||
NX | 4 | 3.369 ± 2.596 | |||
Race | White | 331 | 5.465 ± 2.051 | F = 3.892b | 0.021* |
Asian | 9 | 4.264 ± 2.662 | |||
Black | 28 | 6.304 ± 1.585 | |||
Recurrence | Distant metastasis | 36 | 5.524 ± 2.346 | F = 0.565b | 0.571 |
New primary tumor | 12 | 5.457 ± 2.031 | |||
Locoregional recurrence | 30 | 4.959 ± 2.135 |
LUSC | Non-cancerous tissue | ||||
---|---|---|---|---|---|
Study | Mean ± SD |
n
| Mean ± SD |
n
|
P
|
Hou | 1.118 ± 0.211 | 27 | 0.972 ± 0.135 | 65 | 0.002 |
Garber | 0.752 ± 0.312 | 16 | 0.451 ± 0.146 | 6 | 0.006 |
Wachi | 0.538 ± 0.044 | 5 | 0.507 ± 0.045 | 5 | 0.314 |
Bhattacharjee | 4.141 ± 3.527 | 20 | 2.796 ± 3.070 | 17 | 0.228 |
Talbot | 1.336 ± 0.161 | 34 | 1.503 ± 0.236 | 28 | 0.003 |
Achievement of co-expressed genes
Bioinformatics analysis
Term | Genes | Count | P value |
---|---|---|---|
Focal adhesion | CAV2, CAV1, TNC, COL3A1, ITGA11, PTEN, ITGB1, DOCK1, LAMB2, COL27A1, ITGAV, ILK, COL6A2, COL6A1, PDGFC, PDGFD, LAMB1, THBS1, THBS2, AKT3, FN1, PRKCA, COL4A2, COL4A1, ROCK2, MET, ITGA1, ITGA4, BAD, FLNC, COL5A2, COL5A1, FLNA, LAMA2, VEGFC, LAMA4, ITGA5, COL1A2, PDGFRA, PDGFRB, COL1A1, LAMC1, MYLK, PARVA | 44 | 1.21E−12 |
ECM-receptor interaction | TNC, COL3A1, ITGA11, ITGB1, LAMB2, CD44, ITGAV, COL27A1, COL6A2, COL6A1, THBS1, LAMB1, THBS2, FN1, COL4A2, COL4A1, HSPG2, ITGA1, ITGA4, COL5A2, COL5A1, LAMA2, LAMA4, ITGA5, COL1A2, COL1A1, LAMC1 | 27 | 8.63E−12 |
Proteoglycans in cancer | WNT5A, CAV2, CAV1, WNT5B, MRAS, LUM, TLR4, DCN, MMP2, ITGB1, TIMP3, HOXD10, TGFB1, WNT2, CD44, ITGAV, RRAS, THBS1, FGF2, GPC1, TWIST2, AKT3, FN1, PRKCA, ROCK2, MET, HSPG2, CD63, FLNC, FLNA, PLAUR, PLCE1, ITGA5, ARAF, PTCH1 | 35 | 7.76E−08 |
Pathways in cancer | ADCY3, PPARD, PTGS2, GNA11, PPARG, MITF, LPAR1, MMP2, PTEN, GLI3, TGFB1, EDNRA, WNT2, CDKN2A, FGF2, AKT3, PRKCA, AR, PTGER3, ROCK2, RUNX1T1, VEGFC, PDGFRA, PDGFRB, LAMC1, WNT5A, WNT5B, GNAI1, KITLG, GNG11, GNG12, BDKRB2, ITGB1, LAMB2, ITGAV, RUNX1, LAMB1, TRAF5, FN1, BMP4, IL6, COL4A2, COL4A1, EPAS1, MET, TGFBR2, BAD, LAMA2, LAMA4, ADCY9, RASSF1, ARAF, PTCH1 | 53 | 1.75E−07 |
Amoebiasis | PRKCA, COL4A2, IL6, RAB7B, COL4A1, GNA11, COL3A1, TLR4, COL5A2, TGFB1, COL5A1, LAMA2, LAMA4, LAMB2, COL27A1, COL1A2, HSPB1, COL1A1, LAMC1, LAMB1, FN1 | 21 | 7.93E−06 |
PI3K-Akt signaling pathway | TNC, COL3A1, ITGA11, KITLG, TLR4, GNG11, GNG12, LPAR1, PTEN, ITGB1, LAMB2, COL27A1, ITGAV, COL6A2, CREB3L1, COL6A1, PDGFC, ANGPT1, PDGFD, LAMB1, THBS1, FGF2, THBS2, AKT3, FN1, PRKCA, IL6, COL4A2, COL4A1, MET, ITGA1, ITGA4, BAD, COL5A2, COL5A1, LAMA2, VEGFC, LAMA4, ITGA5, COL1A2, PDGFRA, PDGFRB, COL1A1, LAMC1 | 44 | 1.06E−05 |
Dilated cardiomyopathy | ADCY3, ITGA11, ITGA1, LMNA, CACNB3, ITGA4, TPM2, TPM1, ITGB1, TPM4, TGFB1, ADCY9, ITGA5, ITGAV, SGCD, CACNA1C, SGCB | 17 | 5.69E−05 |
Hypertrophic cardiomyopathy (HCM) | IL6, ITGA1, LMNA, ITGA11, CACNB3, ITGA4, TPM2, TPM1, ITGB1, TPM4, TGFB1, ITGA5, ITGAV, SGCD, CACNA1C, SGCB | 16 | 8.62E−05 |
Protein digestion and absorption | COL4A2, SLC8A1, COL4A1, COL3A1, COL15A1, COL5A2, COL5A1, COL7A1, COL27A1, PRSS3, COL6A2, COL1A2, COL12A1, COL6A1, COL1A1, DPP4 | 16 | 3.50E−04 |
Axon guidance | PLXNA3, NRP1, PLXNA1, ROCK2, GNAI1, MET, NTN4, EPHB3, ITGB1, SLIT2, SLIT3, SEMA5A, CFL2, PPP3CB, SEMA3C, NFATC4, SEMA3B, RHOD, SRGAP1 | 19 | 9.54E−04 |
Node1 | Node2 | Homology | Co-expression | Experimentally determined interaction | Database annotated | Automated text mining | Combined score |
---|---|---|---|---|---|---|---|
PARVA | ILK | 0 | 0.12 | 0.993 | 0.9 | 0.941 | 0.999 |
COL4A1 | COL4A2 | 0.772 | 0.842 | 0.88 | 0.9 | 0.864 | 0.998 |
ITGB1 | ITGA5 | 0 | 0.056 | 0.633 | 0.9 | 0.874 | 0.995 |
COL1A2 | COL1A1 | 0.93 | 0.871 | 0.36 | 0.9 | 0.861 | 0.991 |
COL3A1 | COL1A1 | 0.614 | 0.869 | 0 | 0.9 | 0.823 | 0.99 |
FN1 | ITGAV | 0 | 0 | 0.863 | 0.9 | 0.358 | 0.99 |
COL3A1 | COL1A2 | 0.886 | 0.875 | 0 | 0.9 | 0.781 | 0.988 |
TIMP3 | MMP2 | 0 | 0.082 | 0.528 | 0.8 | 0.871 | 0.987 |
COL1A2 | LUM | 0 | 0.724 | 0.36 | 0.9 | 0.323 | 0.986 |
TGFB1 | DCN | 0 | 0 | 0.387 | 0.9 | 0.797 | 0.986 |
Expression and correlation of hub genes with HOXA11
LUSC | Non-cancerous tissue | ||||
---|---|---|---|---|---|
Mean ± SD |
n
| Mean ± SD |
n
|
P
| |
PARVA | 11.61 ± 0.031 | 502 | 12.25 ± 0.054 | 49 | < 0.001 |
ILK | 8.852 ± 0.032 | 502 | 10.02 ± 0.048 | 49 | < 0.001 |
COL4A1 | 14.15 ± 0.042 | 502 | 14.47 ± 0.159 | 49 | 0.061 |
COL4A2 | 14.33 ± 0.045 | 502 | 14.99 ± 0.138 | 49 | < 0.001 |
ITGB1 | 13.97 ± 0.035 | 502 | 14.42 ± 0.063 | 49 | < 0.001 |
ITGA5 | 12.67 ± 0.047 | 502 | 13.38 ± 0.103 | 49 | < 0.001 |