OBJECTIVES: To explore the mechanism of transforming growth factor-β1 (TGF-β1) induce renal fibrosis. METHODS: Renal fibroblast NRK-49F cells treated with and without TGF-β1 were subjected to RNA-seq analysis. DESeq2 was used for analysis. Differentially expressed genes were screened with the criteria of false discovery rate<0.05 and l o g 2 F C >1. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed for differentially expressed genes. Genes encoding transcription factors were further screened for differential expression genes. Then, the expression of these genes during renal fibrosis was verified using unilateral ureteral obstruction (UUO)-induced mouse renal fibrosis model and a public gene expression dataset (GSE104954). RESULTS: After TGF-β1 treatment for 6, 12 and 24 h, 552, 1209 and 1028 differentially expressed genes were identified, respectively. GO analysis indicated that these genes were significantly enriched in development, cell death, and cell migration. KEGG pathway analysis showed that in the early stage of TGF-β1 induction (TGF-β1 treatment for 6 h), the changes in Hippo, TGF-β and Wnt signaling pathways were observed, while in the late stage of TGF-β1 induction (TGF-β1 treatment for 24 h), the changes of extracellular matrix-receptor interaction, focal adhesion and adherens junction were mainly enriched. Among the 291 up-regulated differentially expressed genes treated with TGF-β1 for 6 h, 13 genes (Snai1, Irf8, Bhlhe40, Junb, Arid5a, Vdr, Lef1, Ahr, Foxo1, Myc, Tcf7, Foxc2, Glis1) encoded transcription factors. Validation in a cell model showed that TGF-β1 induced expression of 9 transcription factors (encoded by Snai1, Irf8, Bhlhe40, Junb, Arid5a, Vdr, Lef1, Myc, Tcf7), while the expression levels of the other 4 genes did not significantly change after TGF-β1 treatment. Validation results in UUO-induced mouse renal fibrosis model showed that Snai1, Irf8, Bhlhe40, Junb, Arid5a, Myc and Tcf7 were up-regulated after UUO, Vdr was down-regulated and there was no significant change in Lef1. Validation based on the GSE104954 dataset showed that IRF8 was significantly overexpressed in the renal tubulointerstitium of patients with diabetic nephropathy or IgA nephropathy, MYC was highly expressed in diabetic nephropathy, and the expressions of the other 7 genes were not significantly different compared with the control group. CONCLUSIONS TGF-β1 induces differentially expressed genes in renal fibroblasts, among which Irf8 and Myc were identified as potential targets of chronic kidney disease and renal fibrosis.
Mice ; Animals ; Humans ; Transforming Growth Factor beta1/metabolism* ; Diabetic Nephropathies/pathology* ; Transcriptome ; Signal Transduction ; Kidney ; Ureteral Obstruction/pathology* ; Fibrosis ; Interferon Regulatory Factors ; Transforming Growth Factor beta/metabolism* ; DNA-Binding Proteins/metabolism* ; Transcription Factors/metabolism*

Objective: To understand the relationship between AOX1, IRF4 gene methylation status in peripheral blood leukocyte DNA, as well as its interaction with environmental factors, and the risk of breast cancer. Methods: A case-control study was conducted among 401 breast cancer patients and 555 cancer-free controls selected from 2010 to 2014. Methylation sensitive-high resolution melting curve analysis was used to detect the methylation status of AOX1 and IRF4. The multiplication interaction effect between genes' methylation and environmental factors on the risk of breast cancer was analyzed by using unconditional logistic regression, and Excel software was used to analyze the additive interaction effect. Results: Individuals without AOX1 methylation had a 1.37-fold (95%CI: 1.02-1.84) higher breast cancer risk compared to individuals with AOX1 methylation. AOX1 methylation interacted with fungi intake (OR=2.06, 95%CI: 1.12-3.79) and physical activity (OR=2.18, 95%CI: 1.16-4.09) synergistically, on the risk for breast cancer, but no additive interaction effects were observed. Non-methylation of IRF4 could increase the risk for breast cancer, with statistical significance (OR=1.71, 95%CI: 0.99-7.43). Neither multiplication nor additive interactions were observed between IRF4 methylation and environmental factors. Conclusion: Non-methylation of AOX1 and IRF4 were a risk factors for breast cancer.
Aldehyde Oxidase/genetics* ; Breast Neoplasms/genetics* ; Case-Control Studies ; DNA Methylation/genetics* ; Female ; Genetic Predisposition to Disease ; Humans ; Interferon Regulatory Factors/genetics* ; Leukocytes/metabolism*

OBJECTIVETo investigate whether Shen-Fu Injection (, SFI) reduces post-resuscitation immune dysfunction in a porcine model of cardiac arrest by modulating apoptosis of regulatory T lymphocytes (Treg) in the spleen.

METHODSAfter 8-min untreated ventricular fibrillation and 2-min basic life support, 24 pigs were divided into 3 groups with a random number table, i.e. SFI group, epinephrine (EP) group, and saline (SA) group (8 in each group), which received central venous injection of SFI (1.0 mL/kg), EP (0.02 mg/kg) and SA, respectively. The same procedure without CA initiation was achieved in the sham-operated (sham) group (n=6). After successful return of spontaneous circulation (ROSC), apoptosis rate of splenic Treg was detected by flow cytometry; and the mRNA expression of forkhead/winged helix transcription factor (Foxp3) of splenic Treg was detected by real time-polymerase chain reaction; and the levels of interleukin-4 (IL-4) and interferon-γ (IFN-γ) in porcine splenic Treg were detected by using enzyme-linked immunosorbent assay (ELISA).

RESULTSCompared with the sham group, the apoptosis rate of Treg was significantly decreased, and the levels of Foxp3 mRNA expression, IFN-γ, IL-4 and IFN-γ/IL-4 were increased in the SA group (P<0.05 or P<0.01). Compared with the EP and SA groups, SFI treatment increased the apoptosis rate of Treg and reduced the levels of Foxp3 mRNA expression, IFN-γ and IFN-γ/IL-4 (P<0.05).

CONCLUSIONSSFI has signifificant effects in attenuating post-resuscitation immune dysfunction by modulating apoptosis of Treg in the spleen.

Animals ; Apoptosis ; drug effects ; Cardiopulmonary Resuscitation ; Disease Models, Animal ; Drugs, Chinese Herbal ; administration & dosage ; pharmacology ; therapeutic use ; Forkhead Transcription Factors ; genetics ; metabolism ; Heart Arrest ; drug therapy ; immunology ; pathology ; physiopathology ; Hemodynamics ; drug effects ; Injections ; Interferon-gamma ; metabolism ; Interleukin-4 ; metabolism ; Lymphocyte Subsets ; drug effects ; metabolism ; Male ; Oxygen ; metabolism ; RNA, Messenger ; genetics ; metabolism ; Spleen ; immunology ; Survival Analysis ; Swine ; Swine, Miniature ; T-Lymphocytes, Regulatory ; drug effects ; immunology

BACKGROUNDPostresuscitation immune dysfunction contributes to the low survival rate after successful resuscitation, but its mechanism remains poorly understood. The purpose of this study was to investigate whether splenic regulatory T-cell (Treg) apoptosis was involved in the postresuscitation immune dysfunction.

METHODSThirty-eight pigs were randomly divided into sham-operated group (SHAM group, n = 8), 12 h post return of spontaneous circulation (ROSC) group, 24 h post-ROSC group, and 48 h post-ROSC group (n = 10 per group). A Wuzhishan miniature porcine model of 8-min ventricular fibrillation cardiac arrest (CA) was established. The apoptosis rates of Treg in the spleen were tested by flow cytometry; the expressions of forkhead/winged helix transcription factor (Foxp3) of Treg in the spleen were detected by real-time polymerase chain reaction; and the levels of interleukin-4 (IL-4), IL-10, and interferon gamma (IFN-γ) of Treg in the spleen were detected by enzyme-linked immunosorbent assay.

RESULTSThe apoptosis rates of Treg in all post-ROSC groups were significantly lower than that of SHAM group (7.7% ± 1.9%, 7.1% ± 1.8%, 6.2% ± 0.4% vs. 13.1% ± 1.6%; P < 0.05); the expression levels of Foxp3 and IL-10 were also decreased with the increase of apoptosis rates of Treg. Helper T-cells CD4+ lymphocyte subsets were significantly lower in the post-ROSC groups compared with SHAM group (29.1% ± 2.2%, 24.3% ± 2.2%, 24.1% ± 2.5% vs. 43.8% ± 4.5%; P < 0.01) at 12, 24, and 48 h after ROSC. Compared with SHAM group, the levels of IFN-γ (161.0 ± 12.9, 167.7 ± 10.5, 191.2 ± 7.7 vs. 7.6 ± 0.9 ng/L) and IL-4 (27.7 ± 6.2, 35.9 ± 3.5, 50.6 ± 6.1 vs. 13.3 ± 2.3 ng/L) and the ratio of IFN-γ/IL-4 (8.6 ± 2.3, 4.9 ± 0.4, 4.5 ± 0.9 vs. 0.8 ± 0.2) were all greatly elevated in all post-ROSC groups (P < 0.05).

CONCLUSIONSApoptosis rate of Treg was significantly decreased after CA, and thus the proportion of Treg was increased and the inhibitory effects were enhanced, which further led to the decrease of the amount of CD4+ T-cells. In addition, the T helper type 2/T helper type 1 (Th2/Th1) cell drift of Treg in the spleen caused postresuscitation immune dysfunction.

Animals ; Apoptosis ; physiology ; Cardiopulmonary Resuscitation ; Disease Models, Animal ; Enzyme-Linked Immunosorbent Assay ; Flow Cytometry ; Forkhead Transcription Factors ; metabolism ; Heart Arrest ; immunology ; metabolism ; Interferon-gamma ; metabolism ; Interleukin-4 ; metabolism ; Random Allocation ; Spleen ; cytology ; Swine ; Swine, Miniature ; T-Lymphocytes, Regulatory ; cytology ; metabolism ; physiology ; Ventricular Fibrillation ; complications ; metabolism

OBJECTIVETo observe the effects of ulinastatin on immune function of splenic CD4(+) T lymphocytes and CD4(+) CD25(+) regulatory T lymphocytes (Tregs) and content of high mobility group box 1 (HMGB1) in peripheral blood of severely burned rats, and to analyze the possible mechanisms.

METHODSNinety-six male SD rats were divided into sham injury group, burn group, and ulinastatin group according to the random number table, with 32 rats in each group. Rats in sham injury group were sham injured on the back by immersing in 37 ℃ warm water for 12 s. Rats in burn group and ulinastatin group were inflicted with 30% total body surface area full-thickness scald (hereinafter referred to as burn) on the back by immersing in 94 ℃ hot water for 12 s. Immediately after injury, rats in each group were intraperitoneally injected with saline (40 mL/kg), meanwhile rats in ulinastatin group were intraperitoneally injected with ulinastatin (4×10(4) U/kg), once per 12 h, till post injury hour 72. Eight rats of each group were respectively selected on post injury day (PID) 1, 3, 5, and 7 to collect abdominal aortic blood samples. Serum content of HMGB1 was detected by enzyme-linked immunosorbent assay (ELISA). And then, rats of the 3 groups were sacrificed immediately to collect spleens and separate CD4(+) CD25(+) Tregs and CD4(+) T lymphocytes. Flow cytometer was used to detect positive expression rates of cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) and forkhead-winged helix transcription factor p3 (Foxp3) in CD4(+) CD25(+) Tregs. Content of IL-10 in culture supernatant of CD4(+) CD25(+) Tregs, and content of interleukin 2 (IL-2), IL-4, and γ interferon (IFN-γ) in culture supernatant of CD4(+) T lymphocytes was detected by ELISA. The proliferative activity of CD4(+) T lymphocytes was determined by microplate reader. The sample number of above-mentioned experiments was 8 at each time point in each group. Data were processed with analysis of variance of factorial design and LSD test.

RESULTS(1) Compared with that in sham injury group, serum content of HMGB1 of rats in burn group was significantly increased from PID 1 to 7 (with P values below 0.01). Compared with that in burn group, serum content of HMGB1 of rats in ulinastatin group was significantly decreased from PID 1 to 7 (with P values below 0.01). (2) Compared with those in sham injury group, the positive expression rates of CTLA-4 and Foxp3 in CD4(+) CD25(+) Tregs and content of IL-10 in culture supernatant of CD4(+) CD25(+) Tregs of rats in burn group were significantly increased from PID 1 to 7 (with P values below 0.01), peaking on PID 3 [(65±10)%, (76±10)%, and (28.2±4.4) pg/mL respectively]. These 3 indexes of rats in sham injury group on PID 3 were (45±7)%, (46±7)%, and (11.2±2.3) pg/mL respectively. Compared with those in burn group, the positive expression rates of CTLA-4 and Foxp3 in CD4(+) CD25(+) Tregs and content of IL-10 in culture supernatant of CD4(+) CD25(+) Tregs of rats in ulinastatin group were significantly decreased from PID 1 to 7 (P<0.05 or P<0.01), reaching the nadir on PID 7 [(43±6)%], PID 1 [(50±8)%], and PID 7 [(12.4±3.4) pg/mL] respectively. These 3 indexes of rats in burn group on PID 7, 1, and 7 were (58±8)%, (71±9)%, and (19.7±2.8) pg/mL respectively. (3) Compared with those in sham injury group, the content of IL-2 and IFN-γ in culture supernatant of CD4(+) T lymphocytes of rats was significantly decreased, while the content of IL-4 in culture supernatant of CD4(+) T lymphocytes of rats was significantly increased in burn group from PID 1 to 7, with P values below 0.01. Compared with that in burn group, the content of IL-2 and IFN-γ in culture supernatant of CD4(+) T lymphocytes of rats was significantly increased, while the content of IL-4 in culture supernatant of CD4(+) T lymphocytes of rats was significantly decreased in ulinastatin group from PID 1 to 7, P<0.05 or P<0.01. (4) Compared with that in sham injury group, the proliferative activity of CD4(+) T lymphocytes of rats in burn group was significantly decreased from PID 1 to 7 (with P values below 0.01). Compared with that in burn group, the proliferative activity of CD4(+) T lymphocytes of rats in ulinastatin group was significantly increased from PID 1 to 7 (with P values below 0.01).

CONCLUSIONSUlinastatin can weaken the immunosuppressive function mediated by splenic CD4(+) CD25(+) Tregs in severely burned rats, and improve proliferative function and secretory function of splenic CD4(+) T lymphocytes, which may be attributed to the inhibiting effect of ulinastatin on the release of HMGB1 in large amount.

Animals ; Burns ; drug therapy ; CTLA-4 Antigen ; metabolism ; Enzyme-Linked Immunosorbent Assay ; Flow Cytometry ; Forkhead Transcription Factors ; metabolism ; Glycoproteins ; pharmacology ; HMGB1 Protein ; blood ; Interferon-gamma ; metabolism ; Interleukin-10 ; metabolism ; Interleukin-2 ; metabolism ; Interleukin-4 ; metabolism ; Male ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Spleen ; drug effects ; T-Lymphocytes, Regulatory ; cytology ; drug effects

BACKGROUNDNon-Hodgkin lymphoma is the fourth most common malignant tumors in children, Burkitt lymphoma (BL) accounts for 30-50% of all pediatric lymphomas. The aim of this study was to investigate the clinicopathologic features, immunophenotype, Epstein-Barr virus (EBV) infection and c-myc gene rearrangement of sporadic BL in children.

METHODSNinety-two cases of pediatric BL were retrospectively analyzed for clinical features, immunohistochemistry, EBV-encoded RNA (EBER) status by in situ hybridization and c-myc gene rearrangement by fluorescence in situ hybridization.

RESULTSIn the 92 cases, male is predominant in sex distribution (M: F = 3.38:1). The average age at diagnosis was 4.97 years. Polypoid BL showed a lower clinical stage (P = 0.002), and advanced clinical stage and low serum albumin level at diagnosis were associated with poor outcome (P = 0.024 and 0.053, respectively). The positive expression of CDl0, B-cell lymphoma-6, MUMl and EBER were 95.7% (88 cases), 92.4% (85 cases), 22.8% (21 cases), 41.3% (38 cases), respectively. The expression of MUM1 were not associated with EBV infection status (P = 1.000). c-myc gene rearrangement was detected in 94.6% (87/92). Clinical treatment information for 54 cases was collected, 21 patients died of tumor after surgery alone, 33 patients received surgery and chemotherapy, and of which six patients died shortly afterwords (MUM1 positive expression in 3 cases, P = 0.076).

CONCLUSIONSThe anatomical location, growth pattern and serum albumin level of BL were associated with biological behavior. MUM1 may be a potential adverse prognostic marker, and not associated with EBV infection status.

Adolescent ; Burkitt Lymphoma ; diagnosis ; epidemiology ; metabolism ; Child ; Child, Preschool ; Epstein-Barr Virus Infections ; diagnosis ; metabolism ; Female ; Humans ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; Infant ; Interferon Regulatory Factors ; metabolism ; Male ; Sex Distribution

ADP-ribosyl Cyclase 1 ; metabolism ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Biomarkers, Tumor ; metabolism ; Biopsy ; Bone Neoplasms ; drug therapy ; metabolism ; pathology ; CD56 Antigen ; metabolism ; Humans ; Ilium ; Interferon Regulatory Factors ; Male ; Middle Aged ; Multiple Myeloma ; drug therapy ; metabolism ; pathology ; Syndecan-1 ; metabolism

OBJECTIVEParkinson's disease (PD), a neurodegenerative disorder, has been reported to be associated with brain neuroinflammation in its pathogenesis. Herein, changes in peripheral immune system were determined to better understand PD pathogenesis and provide possible target for treatment of PD through improvement of immune disorder.

METHODS1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) was intraperitoneally injected into mice to prepare PD model. Expression levels of pro-inflammatory and anti-inflammatory cytokines and transcription factors of CD4+ T lymphocyte subsets in spleen and mesenteric lymph nodes and concentrations of the cytokines in serum were examined on day 7 after MPTP injection. Percentages of CD4+ T lymphocyte subsets were measured by flow cytometry.

RESULTSMPTP induced PD-like changes such as motor and behavioral deficits and nigrostriatal impairment. Expression levels of the pro-inflammatory cytokines including interferon (IFN)-γ, interleukin (IL)-2, IL-17 and IL-22, in spleen and mesenteric lymph nodes were upregulated and their concentrations in serum were elevated in PD progression. But, the concentrations of the anti-inflammatory cytokines including IL-4, IL-10 and transforming growth factor (TGF)-β were not altered in the two lymphoid tissues or serum of PD mice. In addition, expression of T-box in T cells (T-bet), the specific transcription factor of helper T (Th) 1 cells, was downregulated, but expression of transcription factor forkhead box p3 (Foxp3), the transcription factor of regulatory T (Treg) cells, was upregulated. In support of the results, the numbers of IFN-γ-producing CD4+ cells (Th1 cells) were reduced but CD4+CD25+ cells (Treg cells) were elevated in both the lymphoid tissues of PD mice.

CONCLUSIONPD has a dysfunction of peripheral immune system. It manifests enhancement of proinflammatory response and CD4+ T cell differentiation bias towards Treg cells away from Th1 cells.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine ; Animals ; CD4-Positive T-Lymphocytes ; pathology ; Cell Differentiation ; Cytokines ; blood ; Disease Models, Animal ; Flow Cytometry ; Forkhead Transcription Factors ; metabolism ; Interferon-gamma ; blood ; Interleukin-10 ; blood ; Interleukin-17 ; blood ; Interleukin-2 ; blood ; Interleukin-4 ; blood ; Interleukins ; blood ; Lymph Nodes ; cytology ; Lymphocyte Activation ; Mice ; Parkinson Disease ; immunology ; physiopathology ; Spleen ; cytology ; T-Box Domain Proteins ; metabolism ; T-Lymphocytes, Regulatory ; Th1 Cells ; Transforming Growth Factor beta ; blood

OBJECTIVETo investigate the effects of low-concentration ozone exposure on the percentage of CD4(+)CD25(high)Foxp(3+) regulatory T cells and the mRNA expression of transcription factor Foxp3 in asthmatic rats.

METHODSSixty male Wistar rats were randomly divided into 4 groups (n = 15 for each): normal control group, ovalbumin (OVA) exposure group, ozone exposure group, and OVA+ozone exposure group. The OVA exposure group was sensitized and challenged with OVA to establish an asthma model; the normal control group inhaled aerosolized saline; the ozone exposure group inhaled low-concentration ozone; the OVA+ozone exposure group inhaled low-concentration ozone before being challenged with aerosolized OVA every day. The percentage of CD4(+)CD25(high)Foxp(3+) regulatory T cells in CD4(+) T cells was determined by flow cytometry. The levels of interferon-γ (INF-γ) and interleukin 4 (IL-4) in peripheral blood and lung tissue were measured by enzyme-linked immunosorbent assay. The mRNA expression of Foxp3 in lung tissue was measured by PCR.

RESULTSThe percentages of CD4(+)CD25(high)Foxp(3+) regulatory T cells in OVA exposure group (6.12±1.03%) and ozone exposure group (5.87±1.26%) were significantly lower than that in normal control group (9.85±1.34%), and the percentage of CD4(+)CD25(high)Foxp(3+) regulatory T cells in OVA+ozone exposure group (3.31±0.85%) was significantly lower than those in normal control group and OVA exposure group (P < 0.01). The levels of IL-4 in plasma and lung tissue in OVA exposure group (plasma: 21.83±5.12 ng/L; lung tissue: 0.89±0.13 ng/L) were significantly higher than those in normal control group (plasma: 10.58±2.73 ng/L; lung tissue: 0.32±0.11 ng/L) (P < 0.01). The levels of IL-4 in plasma and lung tissue in OVA+ozone exposure group (plasma: 35.47±7.24 ng/L; lung tissue: 1.50±0.42 ng/L) were significantly higher than those in normal control group and OVA exposure group (P < 0.01). The levels of INF-γ in plasma and lung tissue in OVA exposure group (plasma: 61.78±23.45 ng/L; lung tissue: 0.69±0.21 ng/L] were significantly lower than those in normal control group [plasma: 158.89±60.23 ng/L; lung tissue: 1.86±0.29) (P < 0.01). The levels of INF-γ in plasma and lung tissue in OVA+ozone exposure group (plasma: 10.28±2.63 ng/L; lung tissue: 0.41±0.12 ng/L) were significantly lower than those in normal control group and OVA exposure group (P < 0.01). The mRNA expression of Foxp3 was significantly lower in the OVA+ ozone exposure group than in the normal control group (P < 0.05).

CONCLUSIONLow-concentration ozone exposure may decrease the number of CD4(+)CD25(high)Foxp(3+) regulatory T cells and inhibit the mRNA expression of Foxp3 to promote Th1/Th2 imbalance in asthmatic rats, suggesting that ozone exposure may be one of factors that induce asthma attack.

Animals ; Asthma ; metabolism ; Environmental Exposure ; Flow Cytometry ; Forkhead Transcription Factors ; genetics ; metabolism ; Interferon-gamma ; metabolism ; Interleukin-4 ; metabolism ; Lung ; metabolism ; pathology ; Male ; Ozone ; adverse effects ; RNA, Messenger ; genetics ; Rats ; Rats, Wistar ; T-Lymphocytes, Regulatory ; drug effects ; metabolism ; Th1-Th2 Balance

OBJECTIVETo study the relationship between myc gene rearrangement and myc protein expression in diffuse large B cell lymphoma (DLBCL), and their correlation with prognosis.

METHODSOne hundred and six cases of DLBCLs with follow-up data were analyzed using interphase fluorescence in situ hybridization (FISH) technique. Immunophenotyping analysis for CD20, CD3, myc, Mum-1, CD10, bcl-6 was also performed using EnVision immunohistochemistry.

RESULTSThe percentages of tumor cells expressing myc, Mum-1, CD10 and bcl-6 were 70.8%, 56.6%, 21.7% and 26.4%, respectively. Twenty six cases (24.5%) were of GCB type and the rest (75.5%) were of non-GCB (non germinal center) type. The myc rearrangement was identified in 13 (12.3%) of 106 cases. 13 cases showed to be of non-GCB type. There was no correlation between myc rearrangement and myc protein expression. DLBCLs (n = 13) with myc rearrangement showed significantly poorer overall survival (OS) and progression free survival (PFS), with a median OS and PFS time of 4.7 and 3.2 months, respectively (for OS and PFS, P < 0.001). Multivariate analysis using Cox proportional hazard model confirmed that myc rearrangement, ECOG performance status of 2-4, immunophenotyping subgroup and myc protein were independent factors affecting the prognosis and significantly associated with the survival. However, myc rearrangement was the strongest prognostic factor.

CONCLUSIONSDLBCL with myc gene rearrangement is a subgroup of non-GCB DLBCL with poor outcome. It is an independent and useful factor for prognosis in DLBCL. Expression of myc is influenced by many factors and myc rearrangement may be one of these factors.

Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Cyclophosphamide ; therapeutic use ; Disease-Free Survival ; Doxorubicin ; therapeutic use ; Female ; Follow-Up Studies ; Gene Rearrangement, B-Lymphocyte ; Genes, myc ; Humans ; In Situ Hybridization, Fluorescence ; Interferon Regulatory Factors ; metabolism ; Lymphoma, Large B-Cell, Diffuse ; drug therapy ; genetics ; metabolism ; pathology ; Male ; Middle Aged ; Neoplasm Staging ; Neprilysin ; metabolism ; Prednisone ; therapeutic use ; Proportional Hazards Models ; Proto-Oncogene Proteins c-bcl-6 ; metabolism ; Proto-Oncogene Proteins c-myc ; metabolism ; Survival Rate ; Vincristine ; therapeutic use