Table 3.
Summary of the effect of specific molecular features and biomarkers on prognosis and survival.
| Specific Molecular Feature/Biomarker | Effect on Prognosis and Survival | Elaboration on mechanisms | References |
|---|---|---|---|
| Peripheral T cell lymphoma, not otherwise specified (PTCL-NOS) | |||
| GATA3 expression | Reduced 5-year OS of 19% (95CI: 9%-38%) as compared to the TBX-21 subtype | Drives differentiation of mutant T lymphocytes into Th2 subtype Higher burden of chromosomal abnormalities and MYC signals Marginal enrichment of β-catenin, mTOR and PI3K gene signatures |
Iqbal et al. (38) |
| TBX21 expression | Improved 5-year OS of 38% (95CI: 25%-56%) as compared to the GATA3 subtype | Drives differentiation of mutant T lymphocytes into Th1 subtype Enhancement of IFNγ and NF-κB gene signatures |
|
| DNMT3A mutation | DNMT3A-mutant TXB21-positive PTCL-NOS is associated with worse prognosis in CHOP-treated patients, negating the survival benefits of TXB21-positivity | DNMT3A mutations in TBX21-positive PTCL-NOS upregulates CD8+ T-cell genes with cytotoxic function | Herek et al. (43) |
| Angioimmunoblastic T cell lymphoma (AITL) | |||
| PD-1/PD-L1 expression in the tumor environment of AITL | The presence of PD-1/PD-L1 expression in AITL tumor and tumor microenvironment was associated with reduced OS although not statistically significant (p = 0.051) | PD-L1 expression may be induced by EBV, EBV-positivity in AITL might be related to the expression of PD-1/PD-L1 for facilitation in immune evasion | Kim et al. (168) |
| Anaplastic Large Cell Lymphoma (ALCL) | |||
| ALK-positivity | Favorable prognosis and response to first-line chemotherapy and ALK-targeted therapy | Presence of the genomic arrangement of the ALK gene on chromosome 2, commonly associated with t(2;5)(p23;q35) | Ellin et al. (23) |
| ALK-negativity | Reduced prognosis and response to first-line chemotherapy as compared to the ALK-positive subtype | Parkhi et al. (57) Parilla et al. (58) Pedersen et al. (59) Hapgood et al. (60) |
|
| - DUSP22 rearrangements | Favorable clinical outcomes with a 5-year OS of 40-90% | The pathways affected by DUSP22 and TP63 rearrangements are of yet unidentified; have not yet been exploited for targeted therapeutics | |
| - TP63 rearrangements | Poorer clinical outcomes with a 5-year OS of 0-17% | ||
| - ‘triple-negative’ | Associated with a 5-year OS of 33-42% | Seen as a heterogenous group with outcomes between that of DUSP22 and TP63-rearranged ALCL | |
| Extranodal NK/T cell lymphoma, nasal type (NKTCL) | |||
| DDX3X mutation | Presence of the DDX3X mutation predicts poorer prognosis in patients treated with CHOP-based therapy 2-year OS and PFS rates for subjects with mutated DDX3X were 39.4 months (vs 80.8 months in WT DDX3X, p < 0.001) and 23.3 months (vs 81.0 months in WT DDX3X, p < 0.001) |
DDX3X regulates RNA helicase and is closely related to the TP53 tumor suppressor gene Recent studies suggest that DDX3X might be the target of TP53 and could cooperate with TP53 to function as a tumor suppressor |
Jiang et al. (65) Wu et al. (215) |
| EGR1 expression | EGR1 upregulation was consistently identified as able to predict better survival and low-risk patients when correlated via assessment using the PINK scoring system for NKTCL | EGR1 is a regulator of multiple genes including GAS1, CD59, CXCR7, RAMP3, which are indicators of good prognosis Silencing of EGR1 appears to inhibit cellular apoptosis, chemosensitivity, and radiation-induced apoptosis |
Lee et al. (68) |
| PD-L1 expression | The population with ≥78.2% monocytes in blood with PD-L1 positivity had significantly higher OS and PFS than the population with <78.2% monocytes (p = 0.031 and 0.029 for OS and PFS respectively) | PD-L1/PD-1 interaction which suppresses native T cell activation and adaptive T cell mediated cancer cell clearance | Zhang et al. (116) He et al. (117) |
| CD38 expression | Strong expression of CD38 in NKTCL was recognized as an independent adverse prognostic factor for PFS (p = 0.009) | CD38 is expressed at lower levels on normal NK cells and can drive activation and proliferation of lymphocytes when activated | Wang et al. (184) |
| STAT3 mutation and PRDM1 expression | STAT3 mutation and PRDM1 non-expression were both independently associated with inferior OS (p = 0.017 and 0.037 respectively) | JAK3/STAT3 signaling has been recognized as a discriminating pathway in NK/T cell lymphoma and play significant roles in the pathogenesis of NKTCL | Liu et al. (189) |
| Primary cutaneous γδ T cell lymphomas (PCGDTL) | |||
| Cell of origin – Vδ1 or Vδ2; epidermis vs dermis vs subcutaneous tissue | Cells of origin from the epidermis (Vδ1) had significantly better survivals (179 months) as compared to those in the dermis (Vδ1, 31 months) and subcutaneous tissue (Vδ2, 12.75 months) | Differences in the cells of origin are hypothesized to contribute to the heterogeneity of clinical presentations, and give rise to unique clinical states | Daniels et al. (76) |
| EBV-associated PTCLs | |||
| ‘Primary EBV-positive nodal T/NK-cell lymphoma’ (PTCL-EBV) | Tumors classified under PTCL-EBV exhibited significantly shorter median OS (4.6 months vs 14.7 months in NKTCL) | These tumors were identified to be clinically distinct from NKTCL, with low genomic instability, upregulation of NK-κB, IFNγ, IL6-JAK-STAT3, and downregulation of EBV miRNA | Myint Wai et al. (202) |
OS, overall survival; PFS, progression-free survival; CHOP, chemotherapy regimen consisting of cyclophosphamide, doxorubicin, vincristine, prednisolone; EBV, Epstein-Barr virus; WT, wild-type.