Table 3.
Summary of major prognostic biomarkers in DLBCL.
| Prognostic factor | Effect on prognosis | Comments |
|---|---|---|
| Cell of origin (COO) | ||
| ABC by GEP, Lymph2Cx7–19 | UF | |
| Non-GCB by IHC20–31 | UF# | Inferior to GEP in prognostication |
| LMO236–40 | F | |
| Molecular subgroups 45 | ||
| MCD, N1, A53 | UF | |
| BN2, ST2 | F | |
| EZB | F, if DHITsig-negative | |
| UF, if DHITsig-positive | ||
| Somatic hypermutation subgroups 46 | ||
| SHM1, SHM2 | UF | |
| SHM3, SHM4 | F | |
| BCL2 | ||
| Overexpression76,77 | UF# | In absence of MYC overexpression: no effect on OS |
| Rearrangement74,75 | UF# | In absence of MYC rearrangement: no effect on OS |
| MYC | ||
| Overexpression85 | UF# | In absence of BCL2 overexpression: no effect on OS |
| Rearrangement80–85 | UF# | In absence of BCL2 rearrangement: no effect on OS |
| BCL6 | ||
| Overexpression89,90 | F# | Strong correlation with ABC subgroup: potential confounder |
| Rearrangement88 | UF# | Strong correlation with GCB subgroup: potential confounder |
| DH/TH 82,85,93,94 | UF | The role of DH-BCL6 is equivocal.97–110 |
| Non-IG partner gene in MYC rearrangement: no effect in OS101 | ||
| Double-expressor 85,86,107 | UF | |
| DHITsig/MHG 103–105 | UF | |
| TP53 | ||
| Mutations109–111 | UF | |
| Overexpression109,113 | UF# | Overexpression in the absence of TP53 mutation: No association with OS |
| CD5 120–122 | UF | |
| Low CD20 123–125 | UF | |
| CD30 126 | F# | Potential role of brentuximab vedotin, UF in EBER-positive cases |
| Ki-67 114 | UF | |
| TME composition | ||
| GB-like, MS subgroups70 | F | |
| IN, DP subroups70 | UF | |
| Stromal-2 expression9 | UF | |
| Stromal-1 expression9 | F | |
| High CD4*CD8:M2*PD-L1 ratio69 | F | |
| High LAMIS expression56 | UF | |
| VEGFR2/VEGFR147,48 | UF | |
| HIF-1a49 | F | |
| SPARC50,51 | F | |
| MHC-II loss65–68 | UF | |
| PD-L1 (expressed by tumor cells)59–61 | UF | Potential role of immune checkpoint inhibitors |
| PD-1 (expressed in TME)62,63 | F | |
| FOXP353,54 | UF# | |
| Cell-cycle regulation and apoptosis | ||
| BCL2L12127 | UF | |
| BIRC5129 | UF | |
| XIAP128 | UF | |
| Other | ||
| PKCβ137 | UF | |
| p-AKT136 | UF | |
| STAT3138 | UF | |
| Circulating cell-free DNA 142–148 | UF | |
#
Studies show conflicting results regarding the prognostic effect of this biomarker.
ABC, activated B-cell; COO, cell of origin; DH/TH, double/triple-hit lymphomas; DHITsig, double-hit signature; DLBCL, diffuse large B-cell lymphoma; DP, depleted; F, favorable; GB-like, germinal center-like; GCB, germinal center B-cell; GEP, gene-expression profiling; IG, immunoglobulin; IHC, immunohistochemistry; IN, inflammatory; LAMIS, lymphoma-associated macrophage interaction signature; MHG, molecular high-grade; MS, mesenchymal; OS, overall survival; TME, tumor microenvironment; UF, unfavorable.