title: A redox signature score identifies diffuse large B-cell lymphoma patients with a poor prognosis.
abstract: Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease in which approximately 40% of the patients respond well to current chemotherapy, but the prognosis for the other 60% is poor. The Leukemia/Lymphoma Molecular Profiling Project (LLMPP) used microarray technology to define a molecular profile for each of 240 patients with DLBCL and develop a molecular outcome predictor score that accurately predicted patient survival. Data from our laboratory and others suggest that alterations in antioxidant defense enzyme levels and redox environment can be oncogenic and affect the response to glucocorticoid treatment, one of the components of combination chemotherapy regimens for lymphoma. The goal of the current study was to reanalyze the LLMPP microarray data to determine whether the levels of antioxidant defense enzymes and redox proteins were correlated with prognosis in DLBCL. We found that patients with DLBCL with the worst prognosis, according to the outcome predictor score, had decreased expression of catalase, glutathione peroxidase, manganese superoxide dismutase, and VDUP1, a protein that inhibits thioredoxin activity. The data suggest that the patients with the worst prognosis combine a decrease in antioxidant defense enzyme expression with an increase in thioredoxin system function (the redox signature score).
authors.affiliation: Department of Pathology, University of Arizona, Tucson, 85724, USA.
authors.forename: Margaret E
authors.initials: ME
authors.lastname: Tome
authors.forename: David B F
authors.initials: DB
authors.lastname: Johnson
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Rimsza
authors.forename: Robin A
authors.initials: RA
authors.lastname: Roberts
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Grogan
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Miller
authors.forename: Larry W
authors.initials: LW
authors.lastname: Oberley
authors.forename: Margaret M
authors.initials: MM
authors.lastname: Briehl
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000235:genetics; D002352:Carrier Proteins / Q000096:biosynthesis* / Q000235:genetics; D018572:Disease-Free Survival; D020869:Gene Expression Profiling / Q000379:methods; D015973:Gene Expression Regulation, Leukemic; D016393:Lymphoma, B-Cell / Q000188:drug therapy / Q000201:enzymology* / Q000401:mortality; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy / Q000201:enzymology* / Q000401:mortality; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D010084:Oxidation-Reduction; D010088:Oxidoreductases / Q000096:biosynthesis* / Q000235:genetics; D011237:Predictive Value of Tests; D011379:Prognosis; D013879:Thioredoxins / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D000975:Antioxidants; D014408:Biomarkers, Tumor; D002352:Carrier Proteins; C486715:TXNIP protein, human; D013879:Thioredoxins; D010088:Oxidoreductases