Table 2.
Differentially expressed genes in the molecularly defined AITL
| Genes in classifier | Other differentially expressed genes* | |
|---|---|---|
| Cytokine/chemokine signature | ||
| Proinflammatory response | LTA (TNFSF1), LTB (TNFSF3) | IFNαR1, IFNγR1, IFNγR2 |
| T- and B-cell activation | TNFRSF4 (OX40/CD134), TNFRSF17(BCM/CD269) TNFSF8 (CD30L/CD153), CSF2RB (CD131), | IL16, IL3RA, IL7 |
| Chemotactic activity for activated T cells | CCL17, CCL19, CCL20, CCL21,CCL22 | CCL18, CCL26, CXCL9, CXCL10 |
| Angiogenesis | CXCL8 (IL8), CXCL5 | IL8, IL23A |
| Homing of B cells and TFH cells to follicles | CXCL13, its receptor (CXCR5) | |
| Monocytes/macrophage activation | CCR2, CSF2RA, CSF1R, CX3CR1, CXCL12 | |
| Granulocyte activation | CSF2RB, CSF3R | |
| TH1 cells | IL-1α, IL21, IL21R, IL23, IL27Rα, IL2Rγ, (LTF) | |
| TH2 cells | IL4, IL6, IL33, IL4R, IL6R, IL6ST | |
| TNF/TNF-R family members (mainly GC-associated) | TNF, TNFRSF11B, TNFRSF1B, TNFSF10, TNFSF11, TNFRSF13C, TNFSF13B, TNFSF13, TNFSF5 (CD40LG) | |
| Immunosuppressive cytokines | TGFβ1, TGFβR2, IL10Rα, IL10Rβ, | |
| Immunosuppressive activities meditated by nontumor cells | VSTM3,VSIG1, LILRB4, LILRB3, LILRB2, LILRB1, LILRA2, LIFR, LIF | |
| B-cell receptor signaling | CD79a, CD19, FCRL5, CD22 | |
| Immunoglobulin family | IgH, IgK, IgL | |
| B-cell–associated/activation | MS4A1 (CD20), CR1 (CD21), CD23, CD24, CD37, FCRLA, AICD, ID3, SpiB | CD19, BLNK, BANK1, BLK, BTK, BTLA, CD79A, CD79B, LYN, SYK, VAV3, SHB, SHCBP1, SOS1 |
| FDC markers | CR1, CR2 (CD21), CD23, CLU, CD200, C4orf7 | FCGR2B (CD32), FDC-M2 (C4b) |
| Complement system | C1S, C3, C4A, C7 | CR1, CR1L, CR2, C1QBP, C1R, C2, C3, C4BPA, C4A, C5AR1, C7, CFB, CFHR1, CFP |
| Antigen presentation | CTSA, CTSC, CTSD, CTSH, CTSK, CTSS, CTSZ | |
| Germinal center–related genes | ||
| B-cell or T-cell | CD10, BCL6, AICDA, GCET1, CXCR5, CD40, POU2AF1 (BOB1), POU2F2 | |
| T cell–specific genes | ||
| TCR subunits, coreceptor molecules | CD28, CD3δ, CD3ϵ, CD3γ, CD4, CD8α, CD8β) | |
| TCR signaling pathway | LCK, FYN, PTPRC (CD45), NFATC1, NFATC2IP,NFATC | |
| Costimulatory | ICOS | CD28, CD27 |
| Coinhibitory | CTLA4 | PCD1/PD1, BTLA |
| SAP/SLAM interaction | SH2D1A(SAP) CD84, LY9 (CD229/SLAM3),LY108 (SLAM6), SLAMF7 (CRACC) | |
| Miscellaneous genes | SOX8, XKR4, GPR64, PTGDS, NTN2L, PLA2G2D, ALPK2, NT5DC4 | |
| Cell-surface receptors, adhesion molecules | ||
| EDG family | EDG1, EDG2, EDG3, EDG4 | |
| Ephrin receptor subfamily | EPHA2, EPHA3, EPHA4, EPHB1, EPHB2, FGFR2I | |
| Protocadherin family | PCDHAC2, PCDH11X, PCDHA10, PCDHA12 | |
| Cell adhesion molecules | ICAM1, ICAM2 ICAM3, ICAM5, VCAM1 | |
| Proliferation-related genes | ||
| G0 to G1/S phase transition | MCM3AP, MCM5, MCM7, NEK3, NEK6 | |
| Cell-cycle progression/regulation | CCNC, CCND2, CCND3, CNDBP1, CCNG2, CCNI, CCNL1, CCNL2, GSPT2, CDK5R1, CDKN1B | |
| Cell division/ regulation | CDC25B, CDC2L1, CDC2L2, CDC37, CDC42, CDC42BPB, CDC42EP4, CDC42EP5, CDC42SE2, CLK1, CDK2AP2, CIZ1 | |
| Transcription factors (oncogenic activities) | CRK, ERG, ETS1, FGR, FOS, JUN, MET1, MYC,MYB, MAF, PVT1 | |
| Antiapoptosis | BCL2, BCL2A1, BCL2L1, FAIM3 |
CT indicates cytotoxic T cells; IFN, interferon; IL, interleukin; NK, natural killer; PTCL, peripheral T-cell lymphoma; TCR, T-cell receptor; TFH, T-follicular helper; TGF, transforming growth factor; and TNF, tumor necrosis factor.
*
Only up-regulated representative genes are included in each PTCL subtype signature.