Scripties UMCG - Rijksuniversiteit Groningen
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Validation of proteins found by proteomics to distinguish between germinal centers derived and activated B-cell type Diffuse Large B-cell Lymphoma

(2017) Alsagoor, Y. (Yasir)

Diffuse large B-cell lymphoma (DLBCL) is the most common and aggressive non-
Hodgkin lymphoma. Gene expression profiling has subdivided DLBCL into germinal
center B-cell (GCB) and activated B-cell (ABC). Loss of HLA in lymphoma may inhibit
anti-tumor response and is associated with a poor prognosis. A protein profile was made
of primary tumor cells of GCB and ABC subtypes DLBCL and of patients with and
without HLA expression using proteomics. We aim in this study to validate the proteins
with differential expression in distinct DLBCL subtypes and to investigate if there are
differences in immunological response proteins after loss of HLA in DLBCL.
Methods and results
Protein expression immunohistochemistry was conducted on 63 cases, of which 31
ABC’s and 32 GCB’s, 36 with HLA class I positive, 27 with HLA class I negative, 46
with HLA class II positive, 17 with HLA class II negative, 23 with double HLA positive
and 4 with double HLA negative. The expression of ADK and GLMN were significantly
higher in GCB, while ARMC6 and CSNK2A2 were significantly elevated in ABC. Our
analysis also showed a significant higher expression for MAVS in HLA negative
patients. HMOX was not significantly higher expressed in HLA class I and II negative
patients, whereas a trend was noticed in double HLA negative patients. The expression of
PPM1A was not significantly elevated in the negative cases for HLA class I and double
HLA, but significantly elevated in HLA class II. Finally, EIF4G1 expression was not
significant elevated in the positive of HLA class I and double HLA, but significantly
elevated in HLA class II positive cases.
Our research study revealed that the proteins were up or down regulated in the DLBCL
subtypes and in cases with loss of HLA expression. We could for the first time validate
our proteomics data.

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