TABLE 1.
The tumor-associated function of 56 core IRGs.
| Types | No./Gene names | Functions | References |
| Chemokine-related genes | CXC motif chemokine receptor 4 (CXCR4) | Tumor proliferation, angiogenesis, invasion. Migration promoted through MMP-2/MMP-9 or MEK1/2 and ERK1/2 pathways | González-Arriagada et al., 2018 |
| CXC motif chemokine receptor 3 (CXCR3) | Induction of cytoskeletal remodeling and EMT through the AKT pathway, invasion, and metastasis of tongue squamous cell carcinoma | Li Z. et al., 2018 | |
| CXC motif chemokine ligand 13 (CXCL13) | Promotes osteoclast activation and OSCC invasion | Sambandam et al., 2013 | |
| CXC motif chemokine ligand 2 (CXCL2) | Affects the expression of CDK4, cell proliferation in esophageal cancer, Bone destruction | Wang et al., 2009 | |
| CC motif chemokine ligand 26 (CCL26) | Binding to CCR3 receptors increases the expression of IL6 and IL8 and promotes tumor invasion | Sun et al., 2018 | |
| CC motif chemokine receptor 8 (CCR8) | Regulates the function of Treg and promotes tumor migration and invasion | Liu et al., 2019 | |
| Interleukin- related genes | Interleukin1β (IL1β) | The CCL22-CCR4-FOXp3 pathway is involved in tumor genesis and development | Li et al., 2019 |
| Interleukin 21 receptor (IL21R) | Affects the migration of cancer cells through the MMP pathway | León et al., 2015 | |
| Interleukin1α (IL1α) | Participates in the inflammatory process | Li et al., 2019 | |
| Interleukin 34 (IL34) | Promotes the differentiation of monocytes and macrophages, tumor growth, metastasis, and angiogenesis | Endo et al., 2020 | |
| Interleukin 27 receptor subunit α (IL27Rα) | Mediates inflammatory response, T lymphocyte infiltration | Sénécal et al., 2016 | |
| Interleukin 2 receptor subunit γ (IL2Rγ) | Regulates the differentiation of multiple lymphocyte lineages | Goh and Hong, 2017 | |
| Growth factor-related genes | Colony-stimulating factor 2 (CSF2) | GM-CSF stimulates HNSCC cell invasion and metastasis by upregulating MMP-2 and MMP-14 expression | Hong, 2016 |
| Lymphotoxin α (LTα) | Regulating the TNFR/NF-κB signaling pathway mediates PFKF33-dependent glycolysis and promotes tumor angiogenesis of HNSCC | Lauenborg et al., 2015 | |
| TNF receptor superfamily member 12α (TNFRSF12α) | Stimulation of the NF-κB signaling pathway. As a prognostic marker for PTC | Qiu et al., 2018 | |
| TNF receptor superfamily member 25 (TNFRSF25) | Enhanced T cell memory in patients with metastatic HNSCC. Stimulates NF-κB activity and regulates apoptosis | Schreiber et al., 2012 | |
| TNF receptor superfamily member 4 (TNFRSF4) | Activating NF-κB promotes the expression of apoptosis inhibitors BCL2 and BCL2lL1/BCL2-XL, thereby inhibiting apoptosis | Schreiber et al., 2012 | |
| Interferon regulatory factor 9 (IRF9) | The antiproliferative activity of IFN is mediated by the JAK–STAT pathway | Nan et al., 2018 | |
| Inhibin subunit βA (INHβA) | The TGF-β/Smad pathway is activated to regulate EMT | Chen et al., 2019 | |
| Transforming growth factor-β3 (TGF-β3) | The main inducer of EMT, promotes the growth and metastasis of HNSCC | Qin et al., 2016 | |
| Platelet-derived growth factor receptor β (PDGFRβ) | Facilitates the rearrangement of actin cytoskeleton and proliferation of tumor cells | Song et al., 2017 | |
| Endothelin receptor type β (EDNRβ) | Promotes the growth of tumor cells in tongue squamous cell carcinoma by MAPK pathway | Vasaikar et al., 2018 | |
| Platelet-derived growth factor subunit A (PDGFA) | Promotes the proliferation and migration of mesenchymal cells | Song et al., 2017 | |
| Vascular endothelial growth factor C (VEGFC) | Promotes angiogenesis and lymphangiogenesis, immune escape | Miao et al., 2018 | |
| Protease-related genes | Zeta chain of T cell receptor-associated protein kinase 70 (ZAP70) | Bcl-2 expression is upregulated by NF-κB and AKT pathways, promoting tumor metastasis | Gladkikh et al., 2017 |
| Granzyme B (GZMB) | CTL activation is also an important effector molecule of NK cytotoxicity | Mhaidat et al., 2014 | |
| Plasminogen activator, urokinase (PLAU) | Promotes tumor migration and invasion | Magnussen et al., 2014 | |
| Plasminogen activator, urokinase receptor (PLAUR) | Associated with poor prognosis of OSCC | Magnussen et al., 2014 | |
| Proteasome 26S subunit, non-ATPase 2 (PSMD2) | The cell cycle of the G0/G1 phase is regulated by P21 and/or P27 | Li Y. et al., 2018 | |
| T and B cell surface molecule-related genes | CD19 | It forms a complex with CD21 that blocks the B cell receptor signaling pathway | Liu et al., 2020 |
| CD79A | Promotes tumor genesis and metastasis | Luger et al., 2013 | |
| Programmed cell death 1 (PACD1) | Mediated immune escape | Ran and Yang, 2017 | |
| CD22 | CD19 signal transduction is inhibited by B cell receptors and co-receptors | Kim et al., 2020 | |
| Inducible T cell costimulatory (ICOS) | Cell signaling, immune response, and cell proliferation | Fan et al., 2020 | |
| SH2 domain-containing 1A (SH2D1A) | Mediates two-way stimulation of T cells and B cells | Koochakzadeh et al., 2015 | |
| CD247 | As a biomarker for PTC | Ye et al., 2019 | |
| Kinase-related genes | Gastrin (GAST) | Regulates autophagy through the STK11-Prkaa2-ULk1 pathway | Rao et al., 2017 |
| Gonadotropin-releasing hormone 1 (GNRH1) | Participates in the self-renewal and dry maintenance of lung cancer stem cell-like cells through upregulation of the JNK signaling pathway | Lu et al., 2015 | |
| Stanniocalcin1 (STC1) | Promotes apoptosis by phosphorylation of P65 by PI3K/AKT, IκB and IKK signaling | Pan et al., 2017 | |
| Stanniocalcin2 (STC2) | Promotes HNSCC migration by regulating PI3K/AKT/Snail signaling pathway | Xue et al., 2019 | |
| Androgen receptor (AR) | A shorter CAG repeat length in the gene was associated with an adverse outcome in HNSCC | Rosa et al., 2007 | |
| Nuclear receptor subfamily 3 group C member 2 (NR3C2) | Mediates the effect of aldosterone on salt and water balance in restricted target cells | Zhao et al., 2020 | |
| Others | Baculoviral IAP repeat-containing 5 (BIRC5) | Inhibits apoptosis and ensures proper chromosome separation | Frassanito et al., 2019 |
| Pentraxin 3 (PTX3) | Mediates maladjustment of mitotic signaling pathways and tumor escape | Chan et al., 2017 | |
| Pleiotrophin (PTN) | Promotion of tumor proliferation and inhibition of apoptosis-reduced chemotherapy sensitivity | Zhou et al., 2018 | |
| SHC adaptor protein 1 (SHC1) | The immunosuppressive effect of STAT3 was enhanced, and the immune surveillance effect of STAT1 was decreased in breast cancer | Ahn et al., 2017 | |
| Retinol-binding protein 1 (RBP1) | Contributes to the uptake of retinol. Upregulation is associated with poor prognosis in TSCC | Chen et al., 2018 | |
| Progestagen associated endometrial protein (PAEP) | PAEP/glycoprotein stimulates the TGF pathway and PKC cascade. Inhibits T lymphocyte activation, proliferation, and cytotoxicity | Weber et al., 2019 | |
| Surfactant protein A2 (SFTPA2) | Enhances the phagocytosis and chemotaxis of alveolar macrophages | Maitra et al., 2010 | |
| Dickkopf WNT signaling pathway inhibitor 1 (DKK1) | Inhibits WNT signaling and promotes proliferation, invasion, and growth in cancer cell lines | Sun et al., 2019 | |
| Plexin D1 (PLXND1) | Mediates invasion and metastasis of prostate cancer cells through Notch-induced cell migration and regulation of E-cadherin | Vivekanadhan and Mukhopadhyay, 2019 | |
| Semaphorin 3G (SEMA3G) | Inhibition of tumor cell migration and invasion | Zhou et al., 2012 | |
| B cell linker (BLNK) | Inhibits lymphocyte differentiation in tumors, leading to disease progression | Lee et al., 2020 | |
| Secreted LY6/PLAUR domain containing 1 (SLURP1) | Activates cholinergic transmission and promotes T cell development | Bergqvist et al., 2018 | |
| Immunoglobulin heavy chain (including IGHM, IGHV12, IGHV3.64, and IGHV4.34) | IGH gene was significantly correlated with tumor recurrence rate. Different gene rearrangement affects the diversity of immunoglobulin | Thörnqvist and Ohlin, 2018 | |
| T cell receptor α variable region (Including TRAV2, TRAV4, TRAV8.3, TRAV8.6, TRAV26.1, and TRBJ2.3) | TRAV-TRAJ gene recombination is associated with antigen recognition, and the diversity of TRAV genes provides more protective immunity | Pakasticali et al., 2019 |
AKT, serine/threonine kinase; CDK4, cyclin dependent kinase 4; CTL, Cytotoxic T lymphocytes; ERK, Extracellular signal-regulated kinase; HNSCC, head and neck squamous cell carcinoma; IκB, inhibitor of nuclear factor kappa-B; IKK, inhibitor of nuclear factor kappa-B kinase; IRG, immune-related gene; JAK, Janus kinase; MAPK, mitogen-activated protein kinase; MEK, MAP kinase/ERK kinase 1; MMP, matrix metalloproteinase; NF, nuclear factor; NK, natural killer; OSCC, oral squamous cell carcinomas; PFKF, phosphofructokinase; PKC, protein kinase C; PTC, papillary thyroid carcinoma; PI3K, phosphoinositide 3-kinase; STAT, signal transducer and activator of transcription; TNF, tumor necrosis factor; TSCC, tongue squamous cell carcinoma.