Expression of a soluble decoy receptor 3 in patients with diffuse large B-cell lymphoma predicts clinical outcome.
The soluble decoy receptor 3 (DcR3) is a member of the TNF receptor superfamily. It is regarded as a decoy receptor released from tumor cells to escape host immune response by neutralizing the cytotoxic and immunomodulatory effects of FasL, LIGHT and TL1A. Overexpression of DcR3 has been observed in several human malignancies; however, only limited information exists on the role of DcR3 in non-Hodgkin lymphoma especially for B-cell origin. In the current study, the expression profile of DcR3 was analyzed by RT-PCR and immunohistochemistry (IHC) in a set of lymphoma cell lines including T-cell and B-cell lymphomas. The result demonstrated that overexpression of DcR3 was detected in most T-cell lymphoma cells, which was consistent with previous reports. Interestingly, overexpression of DcR3 was also detected both in the B-cell lymphoma cell lines and diffuse large B cell lymphoma (DLBCL) patients. DcR3 overexpression was associated with a worse prognosis in DLBCL patients (p=0.05). An in vitro study showed that neutralization of DcR3 increased the percentage of doxorubicin-mediated apoptosis in two B-cell lymphoma cell lines, which indicated the possibility of DcR3 mediated chemo-resistance in B-cell lymphomas. We suggest that overexpression of DcR3 is associated with a worse prognosis in DLBCL and the possible mechanism may act through the increase of chemo-resistance of lymphoma cells.
Chang
Peter Mu-Hsin
PM
Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan, R O C.
Chen
Po-Min
PM
Hsieh
Shie-Liang
SL
Tzeng
Cheng-Hwai
CH
Liu
Jin-Hwang
JH
Chiou
Tzeon-Jye
TJ
Wang
Wei-Shu
WS
Yen
Chueh-Chuan
CC
Gau
Jyh-Pyng
JP
Yang
Muh-Hwa
MH
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000032:analysis*; D003520:Cyclophosphamide / Q000627:therapeutic use; D004317:Doxorubicin / Q000627:therapeutic use; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D016403:Lymphoma, Large B-Cell, Diffuse / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D016399:Lymphoma, T-Cell / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011241:Prednisone / Q000627:therapeutic use; D011379:Prognosis; D053323:Receptors, Tumor Necrosis Factor, Member 6b / Q000096:biosynthesis*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014750:Vincristine / Q000627:therapeutic use
D014408:Biomarkers, Tumor; D053323:Receptors, Tumor Necrosis Factor, Member 6b; C505911:TNFRSF6B protein, human; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone