Table 6.
Top significantly upregulated and downregulated genes in alveolar/bronchiolar carcinomas (ABCs) from B6C3F1/N mice exposed to Antimony trioxide for 2 years as determined by Ingenuity Pathway Analysis (IPA).
| Gene | Description | Fold Change | Relevance to Cancer |
|---|---|---|---|
|
| |||
| Top twenty up-regulated genes | |||
| Dlk1 | delta like non-canonical Notch ligand 1 | 209.864 | Highly expressed in NSCLC;43 overexpression promotes lung cancer cell invasion 44 |
| Tmem27 | transmembrane protein 27 | 203.919 | Role unclear in cancer |
| Rian (Meg8) | RNA imprinted and accumulated in nucleus | 66.389 | RNA gene associated with EMT of lung and pancreatic cancer cells 46 |
| Ctse | cathepsin E | 44.964 | Expression associated with pancreatic cancer;48 upregulated and hypomethylated in lung adenocarcinoma 49 |
| Npy2r | neuropeptide Y receptor Y2 | 36.513 | Possible epigenetic marker in oral cancer 60 |
| Serpinb5 | serpin family B member 5 | 33.006 | Tumor suppressing function in lung and breast cancer 61 |
| Moxd1 | monooxygenase DBH like 1 | 12.845 | Role unclear in cancer |
| Mycn | v-myc avian myelocytomatosis viral oncogene neuroblastoma derived homolog | 12.829 | Documented oncogene; overexpressed in NSCLC 50 |
| Fras1 | Fraser extracellular matrix complex subunit 1 | 11.991 | Migration and invasiveness of A549 cells reduced by Fras1 knockdown 62 |
| Ptprn2 | protein tyrosine phosphatase, receptor type N2 | 9.463 | Possible biomarker in lung cancer 63 |
| Smarca1 | SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a, member 1 | 8.232 | Associated with proliferation and migration in colorectal cancer 64 |
| Depdc7 | DEP domain containing 7 | 6.834 | Found to inhibit cell proliferation and cell growth in hepatoma cells 65 |
| Myom2 | myomesin 2 | 6.642 | Role unclear in cancer |
| Cldn4 | claudin 4 | 6.590 | Overexpressed in ovarian cancer 66 and pancreatic cancer 67 |
| Cpne4 | copine 4 | 6.504 | Role unclear in cancer |
| Ddc | dopa decarboxylase | 6.219 | Role unclear in cancer |
| Scara3 | scavenger receptor class A member 3 | 6.091 | Highly expressed in ovarian cancer 68 |
| Mlana | melan-A | 5.670 | Role unclear in cancer |
| Mcpt2 | mast cell protease 2 | 5.631 | Role unclear in cancer |
| Hhex | hematopoietically expressed homeobox | 5.507 | Role unclear in cancer |
| Top twenty down-regulated genes | |||
| Cyp2b6 | cytochrome P450 family 2 subfamily B member 6 | −112.085 | Expressed in human lung;69 may activate NNK 70 |
| Cbr2 | carbonyl reductase 2 | −23.290 | Role unclear in cancer |
| Scgb1a1 (CC10) | secretoglobin family 1A member 1 | −21.666 | May play protective role in lung tumorigenesis induced by NNK, a potent carcinogen 51 |
| Kcnk2 | potassium two pore domain channel subfamily K member 2 | −16.596 | Under-expressed in hepatocellular carcinoma cells 71 |
| Ripply3 | ripply transcriptional repressor 3 | −13.770 | Role unclear in cancer |
| Sdpr | serum deprivation response | −13.055 | Suppresses metastasis in breast cancer; 72 under-expressed in NSCLC 73 |
| Cftr | cystic fibrosis transmembrane conductance regulator | −12.483 | Downregulated in NSCLC; 74 DNA methylation may play role in downregulation of Cftr gene expression 75 |
| Cyp2e1 | cytochrome P450 family 2 subfamily E member 1 | −12.311 | Wild-type allele of Cyp2e1 associated with better survival in NSCLC patients 76 |
| Cfap54 | cilia and flagella associated protein 54 | −12.166 | Role unclear in cancer |
| Hdgfrp3 | hepatoma-derived growth factor, related protein 3 | −10.179 | Upregulated in hepatocellular carcinoma 77 |
| Pigr | polymeric immunoglobulin receptor | −9.818 | Downregulation associated with early lung tumorigenesis, overexpression of Pigr inhibits lung cancer cell proliferation 78 |
| Ntn4 | netrin 4 | −8.661 | Role in suppressing liver metastasis of colo-rectal carcinoma 79 |
| Cfap45 (CCDC19 ) | cilia and flagella associated protein 45 | −6.774 | Potential tumor suppressor, downregulation associated with poor NSCLC prognosis 80 |
| Mme | membrane metalloendopeptidase | −6.116 | High expression related to poor survival in NSCLC patients;81 under-expressed in lung adenocarcinoma 82 |
| Irx2 | iroquois homeobox 2 | −5.979 | Role in suppressing chemokine expression and cell motility in breast cancer 83 |
| Fam65b | family with sequence similarity 65 member B | −5.965 | Overexpression can block proliferation of transformed and primary T cells 84 |
| Dnaja4 | DnaJ heat shock protein family (Hsp40) member A4 | −5.462 | Role unclear in cancer |
| Il2rj | interleukin 2 receptor subunit gamma | −5.208 | Role unclear in cancer |
| Ifit3 | interferon induced protein with tetratricopeptide repeats 3 | −5.187 | Inhibits growth of lung cancer cells by suppressing STAT3 85 |
| Rragd | Ras related GTP binding D | −5.067 | Found to be downregulated in melanoma metastasis samples 86 |
Note: Statistical Significance is set at p < .001 by Fisher’s exact test.