Table 5 Overview of molecular signatures in DLBCL-NOS associated with poor prognosis

Oxidative phosphorylation

GCB (46 %)

ABC (18 %)

type-3 (36 %)

(n.c.i.)

5y OS: 53 %

Oxidative phosphorylation (↑)

TCA cycle (↑)

Lipogenesis (↑)

Glycolytic flux (↓)

Proteosomal activity (↑)

BCR signaling (↓)

Fatty acid metabolism, PPARγ, γ-glutamyl cysteine synthase,

[97, 116, 122, 123, 134]

BCR/proliferation

GCB (23.4 %)

ABC (53.2 %)

type-3 (23.4 %)

(n.c.i.)

5y OS: 60 %

BCR signaling (↑)

NF-κB signaling (↑)

BCL6 (↑)

Proliferation genes (↑)

BTK, PI3K, mTORC1/2, BCL6, BCL2, STAT3, NF-κB

[98, 116, 133, 134, 312, 314]

Host response

GCB (46 %)

ABC (18 %)

type-3 (36 %)

(n.c.i.)

5y OS: 54 %

TCR signaling (↑)

STAT1 signaling (↑)

NF-κB signaling (↑)

PD-1, STAT1, DTX3L, ARTD9

NF-κB, BCL2

[116, 134, 340, 344–346, 469, 470, 472]

C-MYC-driven

GCB (35-50 %)

ABC (45-55 %)

type-3 (5-10 %)

(n.c.i.)

5y OS: ≤40 %

(ABC!)

(n.c.i.)

c-MYC (↑)

Proliferation genes (↑)

BCL2 (↑)

(BCL6) (↑)

Anti-apoptotic signaling (↑)

BRD2 and 4, PRPS2

BCL2, (BCL6)

[107, 119, 138–144, 150, 399, 414]

Stromal-II

Independent of COO(n.c.i.)

n.c.i.

Endothelial markers (↑) Key regulators of angiogenesis (↑)

CXCR4/CXCL12 axis, VEGFR2

[85]

CDKN2A/2B

(9p21) deletion

GCB (4 %)

ABC (30 %)

(n.c.i.)

n.c.i.

Loss of p15INK4B, p16INK4A,

p14ARF,

Loss of RB1/E2F regulation,

Proliferation genes (↑)

Cellular metabolism (↑)

Immune and inflammatory response (↓)

[13, 120, 623]

RCOR1-(TRAF3)-deletion

GCB (15 %) ABC (15 %) (n.c.i.)

5y OS: 55 %

Non-canonical NF-κB signaling (↑) Loss of RCOR1 signaling HDAC class II signaling (↓)

NF-κB, NIK

[27, 121, 160]