Introduction
No. | Gene symbol | Gene Ida
| Gene product official name (aliases) | Gene product functions | References |
---|---|---|---|---|---|
1. |
AGFG1/HRB
| 5175 | Arf-GAP domain and FG repeats containing protein 1 | Probably mediates nucleocytoplasmic transport | |
2. |
STC1
| 11373 | Stanniocalcin 1 | Probably regulates calcium/phosphate transport and metabolism | |
3. |
SLC2A1
| 11005 | Solute carrier family member 2 (facilitated glucose transporter), member 1 | A major glucose transporter in the mammalian blood–brain barrier | |
4. |
CHKA
| 1937 | Choline kinase alpha | Catalyzes the first step in phosphatidylcholine biosynthesis and contributes to phosphatidylethanolamine biosynthesis | [10] |
5. |
CXCL1
| 4602 | Chemokine (C-X-C motif) ligand1 (melanoma growth stimulating activity, alpha) | Recruits neutrophil polymorphonuclear leukocytes at sites of inflammation; stimulates angiogenesis | |
6. |
CXCL2
| 4603 | Chemokine (C-X-C motif) ligand 2 (melanoma growth stimulating activity, beta) | Recruits neutrophil polymorphonuclear leukocytes at sites of inflammation; stimulates angiogenesis | [11] |
7. |
CXCL3
| 4604 | Chemokine (C-X-C motif) ligand 3 (melanoma growth stimulating activity, gamma) | Recruits neutrophil polymorphonuclear leukocytes at sites of inflammation; stimulates angiogenesis | |
8. |
CXCL5
| 10642 | Chemokine (C-X-C motif) ligand5(epithelial-derived neutrophil activating protein 78 (ENA-78)) | Involved in neutrophil activation; stimulates angiogenesis | [11] |
9. |
CXCL6
| 10643 | Chemokine (C-X-C motif) ligand 6 (granulocyte hemotactic peptide-2 (GCP-2)) | Is a chemoattractant for neutrophil granulocytes; stimulates tumor cell growth | [11] |
10. |
CXCR2
| 6027 | Chemokine (C-X-C motif) receptor 2 (interleukin-8 receptor, beta) | Membrane receptor that binds chemokines CXCL6 and CXCL8 with high affinity | [11] |
11. |
CXCR3
| 4540 | Chemokine (C-X-C motif) receptor 3 | Membrane receptor that binds chemokines CXCL9, CXCL10, and CXCL11 | [11] |
12. |
CXCR4
| 2561 | Chemokine (C-X-C motif) receptor 4 | Membrane receptor specific for chemokine CXCL12/SDF-1. Important in the metastatic behavior of solid tumors | |
13. |
CXCL9
| 7098 | Chemokine (C-X-C motif) ligand 9 (monokine induced by gamma interferon (MIG)) | Is a Th1-cell attracting chemokine; blocks angiogenesis | |
14. |
CXCL10
| 10637 | Chemokine (C-X-C motif) ligand 10 (10 kDa interferon-gamma-induced protein (IP-10)) | Is chemotactic for monocytes and T\ lymphocytes, has pleiotropic effects on these cells, and blocks angiogenesis | [11] |
15. |
CXCL11
| 10638 | Chemokine (C-X-C motif) ligand 11 (0Interferon-inducible T cell alpha chemoattractant (I-TAC)) | Is a chemoattractant to interleukin-activated T cells; blocks angiogenesis | [11] |
16. |
CXCL12
| 10672 | Chemokine (C-X-C motif) ligand 12 (Stromal cell-derived factor 1 (SDF-1)) | Is a chemoattractant to T lymphocytes and monocytes | |
17. |
IL10
| 5962 | Interleukin-10 (cytokine synthesis inhibitory factor (CSIF)) | Inhibits the synthesis of a number of cytokines including interferon-gamma, IL-2, IL-3,TNF, and Gm-CSF produced by activated macrophages and by helper T cells | |
18. |
IL6
| 6018 | Interleukin-6 (interferon, beta 2(IFNB2)) | A cytokine that functions in inflammation and the maturation of B cells and is a potent inducer of the acute phase response | [15] |
19. |
IL8
| 6025 | Interleukin-8 (Chemokine (C-X-C motif) ligand 8(CXCL8)) | One of the major mediators of the inflammatory response; stimulates angiogenesis | |
20. |
TNF
| 11892 | Tumor necrosis factor (TNF superfamily, member 2) | A multifunctional pro-inflammatory cytokine involved in the regulation of a wide spectrum of cellular processes, including proliferation, differentiation, and apoptosis | [15] |
21. |
ITGA5
| 6141 | Integrin, alpha 5 (Fibronectin receptor, alpha polypeptide) | A member of integrin family of membrane receptors involved in cell adhesion | [17] |
22. |
ITGB3
| 6156 | Integrin, beta 3 (platelet glycoprotein IIIa, AntigenCD61) | A member of integrin family of membrane receptors involved in cell adhesion | [17] |
23. |
ITGB1
| 6153 | Integrin, beta 1 (Fibronectin receptor) | A member of integrin family of membrane receptors involved in cell adhesion | [17] |
Materials and Methods
Patients and samples
RNA extraction
mRNA expression level
Statistical analysis
Results
Patient characteristics
Differential gene expression between tumor and non-tumor lung tissues
Gene symbol | All NSCLC | SqCC vs. LCC | AdC vs. LCC | ||||
---|---|---|---|---|---|---|---|
Samples (N) | Log-fold-changea mean ± SD |
p-valueb
| Log-fold-change difference mean ± SD |
p-value | Log-fold-change difference mean ± SD |
p-value | |
AGFG1
| 98 | −0.0298 ± 0.1226 |
0.00011
| 0.124 ± 0.0278 |
0.00004
| 0.0564 ± 0.0293 | 0.11439 |
CHKA
| 88 | −0.0235 ± 0.1371 |
0.00004
| 0.159 ± 0.0311 |
0.00001
| 0.0545 ± 0.0322 | 0.18784 |
CXCL1
| 70 | −0.0438 ± 0.1461 |
0.00045
| 0.141 ± 0.0324 |
0.00006
| 0.0695 ± 0.0339 | 0.08631 |
CXCL10
| 69 | −0.0492 ± 0.1558 |
0.00001
| 0.179 ± 0.0355 |
0.00001
| 0.0799 ± 0.0366 | 0.06389 |
CXCL11
| 100 | 0.0040 ± 0.1412 |
0.00001
| 0.173 ± 0.0386 |
0.00004
| 0.0700 ± 0.0397 | 0.16256 |
CXCL12
| 100 | −0.0283 ± 0.1418 |
0.00010
| 0.163 ± 0.0313 |
0.00001
| 0.0620 ± 0.0327 | 0.12277 |
CXCL2
| 102 | 0.0613 ± 0.1436 |
0.00001
| 0.145 ± 0.0322 |
0.00004
| 0.0343 ± 0.0341 | 0.63402 |
CXCL3
| 84 | 0.0385 ± 0.1357 |
0.00001
| 0.143 ± 0.0318 |
0.00004
| 0.0197 ± 0.0334 | 1.00000 |
CXCL5
| 74 | 0.0493 ± 0.1658 |
0.01198
| 0,122 ± 0.0465 | 0.02066 | 0.0355 ± 0.0474 | 0.91205 |
CXCL6
| 19 | −0.0247 ± 0.1674 | 0.13503 | 0.181 ± 0.0719 | 0.02940 | 0.1365 ± 0.0763 | 0.15835 |
CXCL9
| 93 | −0.0723 ± 0.1449 |
0.00001
| 0.143 ± 0.0342 |
0.00013
| 0.0546 ± 0.0359 | 0.26377 |
CXCR2
| 47 | 0.0485 ± 0.1626 | 0.18719 | −0.564 ± 0.3973 | 0.31830 | −0.6288 ± 0.4194 | 0.27431 |
CXCR3
| 26 | −0.0114 ± 0.1613 |
0.00122
| 0.245 ± 0.0503 |
0.00002
| 0.1259 ± 0.0510 |
0.03375
|
CXCR4
| 97 | −0.0278 ± 0.1358 |
0.00003
| 0.154 ± 0.0311 |
0.00001
| 0.0667 ± 0.0326 | 0.08614 |
IL10
| 44 | −0.0485 ± 0.1400 | 0.09305 | 0.119 ± 0.0448 | 0.01949 | 0.0378 ± 0.0460 | 0.82759 |
IL6
| 103 | 0.0403 ± 0.1527 |
0.00007
| 0.153 ± 0.0349 |
0.00005
| 0.0585 ± 0.0368 | 0.22936 |
IL8
| 101 | 0.0075 ± 0.1340 |
0.02278
| 0.111 ± 0.0326 |
0.00196
| 0.0396 ± 0.0345 | 0.50733 |
ITGA5
| 103 | 0.0085 ± 0.1146 |
0.00407
| 0.109 ± 0.0265 |
0.00015
| 0.0448 ± 0.0280 | 0.22635 |
ITGB1
| 105 | −0.0314 ± 0.1224 |
0.00001
| 0.140 ± 0.0267 |
0.00001
| 0.0511 ± 0.0281 | 0.14398 |
ITGB3
| 94 | −0.0228 ± 0.1660 |
0.00005
| 0.194 ± 0.0369 |
0.00001
| 0.0806 ± 0.0388 | 0.07992 |
SLC2A1
| 83 | −0.1353 ± 0.1320 |
0.00001
| 0.079 ± 0.0325 | 0.03216 | 0.0831 ± 0.0342 | 0.03384 |
CTC1
| 88 | −0.0189 ± 0.1265 |
0.00018
| 0.139 ± 0.0296 |
0.00002
| 0.0565 ± 0.0307 | 0.13756 |
TNFA
| 4 | −0.0009 ± 0.1956 |
0.01730
| 0.342 ± 0.0792 |
0.00533
| 0.1721 ± 0.0548 |
0.01745
|
Analysis of overall survival
Variable | Overall survival | Disease-free survival | ||||
---|---|---|---|---|---|---|
Hazard ratio |
p-value | 95 % Confidence interval | Hazard ratio |
p-value | 95 % Confidence interval | |
Age | 1.0057 | 0.787 | 0.9652–1.0478 | 1.0099 | 0.573 | 0.9757–1.0453 |
Gender | 0.5145 | 0.121 | 0.2221–1.1916 | 0.6242 | 0.182 | 0.3126–1.2466 |
TNM II | 9.8231 |
<0.001
| 3.7889–25.4677 | 3.1955 |
<0.001
| 1.6640–6.1366 |
AdC | 1.3598 | 0.444 | 0.6190–2.9874 | 1.4219 | 0.297 | 0.7333–2.7573 |
LCC | 1.9305 | 0.122 | 0.8386–4.4440 | 1.4579 | 0.321 | 0.6923–3.0703 |