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Proteomic profiling identifies outcome-predictive markers in patients with peripheral T-cell lymphoma, not otherwise specified

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  • Maja Ludvigsen
  • Martin Bjerregård Pedersen
  • Kristina Lystlund Lauridsen
  • Tim Svenstrup Poulsen
  • Stephen Jacques Hamilton-Dutoit
  • Søren Besenbacher
  • Knud Bendix
  • Michael Boe Møller
  • Peter Nørgaard
  • Francesco d'Amore
  • Bent Honoré
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Peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) constitutes a heterogeneous category of lymphomas, which do not fit into any of the specifically defined T-cell lymphoma entities. Both the pathogenesis and tumor biology in PTCL-NOS are poorly understood. Protein expression in pretherapeutic PTCL-NOS tumors was analyzed by proteomics. Differentially expressed proteins were compared in 3 distinct scenarios: (A) PTCL-NOS tumor tissue (n = 18) vs benign lymphoid tissue (n = 8), (B) clusters defined by principal component analysis (PCA), and (C) tumors from patients with chemosensitive vs refractory PTCL-NOS. Selected differentially expressed proteins identified by proteomics were correlated with clinico-pathological features and outcome in a larger cohort of patients with PTCL-NOS (n = 87) by immunohistochemistry (IHC). Most proteins with altered expression were identified comparing PTCL-NOS vs benign lymphoid tissue. PCA of the protein profile defined 3 distinct clusters. All benign samples clustered together, whereas PTCL-NOS tumors separated into 2 clusters with different patient overall survival rates (P = .001). Differentially expressed proteins reflected large biological diversity among PTCL-NOS, particularly associated with alterations of "immunological" pathways. The 2 PTCL-NOS subclusters defined by PCA showed disturbance of "stress-related" and "protein metabolic" pathways. α-Enolase 1 (ENO1) was found differentially expressed in all 3 analyses, and high intratumoral ENO1 expression evaluated by IHC correlated with poor outcome (hazard ratio, 2.09; 95% confidence interval, 1.17-3.73; P = .013). High expression of triosephosphate isomerase (TPI1) also showed a tendency to correlate with poor survival (P = .057). In conclusion, proteomic profiling of PTCL-NOS provided evidence of markedly altered protein expression and identified ENO1 as a novel potential prognostic marker.

OriginalsprogEngelsk
TidsskriftBlood advances
Vol/bind2
Udgave nummer19
Sider (fra-til)2533-2542
Antal sider10
ISSN2473-9529
DOI
StatusUdgivet - 9 okt. 2018

ID: 56605111