Table 4.
36 up- and downregulated common DEGs in B16 melanoma shared by PCSK9-WT and D374Y in comparison to control
| Gene | Gene name | Log2 FC | Functions in melanomac | Ref |
|---|---|---|---|---|
| Eda2r | ectodysplasin A2 receptor | 1.46a, 1,75b | EDA2R expression was negatively correlated with prognosis | [69] |
| Ldhd* | lactate dehydrogenase D | 1.34, 1,45 | NA | |
| Car3* | carbonic anhydrase 3 | 1.09, 3.28 | NA | |
| Arg1* | arginase | 1.09, 2.36 | Enhancing activities promoting melanoma | [70] |
| Cnr2* | carbonyl reductase 2 | 1.05, 1.44 | NA | |
| Cd5l | CD5 antigen-like | 0.96, 2.99 | NA | |
| Agap2* | ArfGAP with GTPase domain, ankyrin repeat and PH domain 2 | 0.95, 1.13 | Identified as part of a 6-gene prognostic factor for melanoma patients, AGAP2 was highly expressed in melanoma tissues compared with normal healthy control (p < 0.05, Student’s t-test, n = 10) | [71] |
| Gm16316 | predicted gene 16316 | 0.95, 1.68 | NA | |
| Serpinb8* | serine (or cysteine) peptidase inhibitor, clade B, member 8 | 0.87, 2.19 | NA | |
| Gpx3 | glutathione peroxidase 3 | 0.87, 1.90 | Inhibition of melanoma via inhibiting HIF1-α; negative association with poor prognosis in melanoma patients | [72] |
| Epha5 | Eph receptor A5 | 0.84, 1.99 | High EphA5 expression is associated with longer overall survival time | [73] |
| H19 | H19, imprinted maternally expressed transcript | 0.83, 1.89 | Facilitating melanoma pathogenesis | [74] |
| Fcgr2b* | Fc receptor, IgG, low affinity IIb | 0.83, 1.85 | Suppressing CD8 + T cells-derived cytotoxic actions in patients with melanoma | [75] |
| Omg* | oligodendrocyte myelin glycoprotein | 0.83, 2.22 | NA | |
| Cryzl2 | crystallin zeta like 2 | 0.83, 1.80 | NA | |
| Sgk1* | serum/glucocorticoid regulated kinase 1 | 0.81, 1.12 | Facilitating CD4 + cell differentiation via regulating IL4 and IFN-γ | [76] |
| Gimap7* | GTPase, IMAP family member 7 | 0.80, 1.56 | NA | |
| Slco2a1 | solute carrier organic anion transporter family, member 2a1 | 0.78, 1.53 | NA | |
| Il33* | interleukin 33 | 0.78, 1.45 | Likely contributing to immunosuppressive TME in metastatic melanoma | [77] |
| Tbc1d9* | TBC1 domain family, member 9 | 0.77, 1.37 | NA | |
| Dapk1* | death associated protein kinase 1 | 0.76, 1.50 | A pro-apoptotic factor in melanoma cells | [78] |
| Loxl1 | lysyl oxidase-like 1 | 0.76, 1.62 | NA | |
| F7 | coagulation factor VII | 0.73, 3.68 | NA | |
| Gas6 | growth arrest specific 6 | 0.72, 1.71 | Facilitating activation of MAPK/ERK, PI3K/Akt and JAK/STAT | [79] |
| Selenop (SELP)* | selenoprotein P | 0.70, 1.02 | NA | |
| Saa3 | serum amyloid A 3 | 0.70, 2.53 | NA | |
| Lbp* | lipopolysaccharide binding protein | 0.70, 1.97 | NA | |
| Dpp4* | dipeptidylpeptidase 4 | 0.66, 1.58 | Loss of DPP4 associates with melanoma progression | [80] |
| Cyp27a1* | cytochrome P450, family 27, subfamily a, polypeptide 1 | 0.60, 2.63 | Cyp27a1 is a transcriptional target of melanogenesis-associated transcription factor (MITF). Cyp27a1 is necessary for the generation of a reactive metabolite that inhibits cellular proliferation in melanoma | [81] |
| Itga6* | integrin alpha 6 | -0.63, -1.38 | Decrease in metastatic SKCM tissues correlates with immune cell infiltration; Iga6 expression was also remarkably negatively correlated with overall survival in SKCM patients | [82] |
| Scn1a | sodium channel, voltage-gated, type I, alpha | -0.81, 1.19 | NA | |
| Tenm4 | teneurin transmembrane protein 4 | -0.82, -2.50 | Lower TENM4 mRNA levels have been observed in skin cutaneous melanoma (TCGA dataset & GTEx project) compared to normal tissues | [83] |
| Garnl3 | GTPase activating RANGAP domain-like 3 | -0.93, -1.67 | NA | |
| Slc4a4 | solute carrier family 4 (anion exchanger), member 4 | -0.95, -2.23 | NA | |
| Tnfrsf9* | tumor necrosis factor receptor superfamily, member 9 | -0.97, -1.61 | As a costimulatory receptor in immune cells, TNFRSF9 enhances immune cell infiltration. Furthermore, elevated TNFRSF9 mRNA expression and TNFRSF9 hypomethylation correlated with improved overall survival. In patients receiving anti-PD-1 immunotherapy, reductions of TNFRSF9 correlated with poor response | [84] |
| Miga1 | mitoguardin 1 | -2.52, -3.71 | NA |
a: PCSK9 vs EV
b: D374Y vs EV
c: for human homologue genes of mouse 36 overlapped DEGs
*: component genes of Overlap36sub