title: Downregulated expression of Dicer1 predicts inferior survival in primary gastrointestinal diffuse large B-cell lymphoma treated with CHOP-like regimen and rituximab.
abstract: The aim of this study was to detect the expression levels of Dicer1, Drosha, DGCR8, and Ago2 messenger ribonucleic acids (mRNAs) in patients with primary gastrointestinal diffuse large B-cell lymphoma (PGI-DLBCL) and determine their associations with clinical parameters and prognostic significance. The mRNA level expressions of Dicer1, Drosha, DGCR8, and Ago2 were detected by real-time quantitative polymerase chain reaction. Immunohistochemical staining of CD10, BCL6, and MUM1 was performed using EnVision™ system. The clinicopathologic features and follow-up data were analyzed using Kaplan-Meier estimator. The results show that the expression of Dicer1 (P=0.001), Drosha (P=0.01), DGCR8 (P=0.02), and Ago2 (P=0.002) mRNAs in cancer tissues of patients with PGI-DLBCL was significantly lower than those in normal tissues of healthy controls. Among the expression of CD10, BCL6, and MUM1, 27.4% (17/62) of the patients belonged to the germinal center B-cell (GCB) subtype and 72.6% (45/62) belonged to the non-GCB subtype. Dicer1 expression was significantly decreased in the non-GCB subgroup (P=0.02) and in the high International Prognostic Index (3-5 score) subgroup (P=0.03). Kaplan-Meier analysis showed that the low-Dicer1 subgroup had a shorter overall survival (P=0.02) and shorter progression-free survival (P=0.015) than the high-Dicer1 subgroup. Multivariate analysis identified Dicer1 as an independent prognostic factor in PGI-DLBCL. In Conclusion, Dicer1, Drosha, DGCR8, and Ago2 play key roles in the pathogenesis of PGI-DLBCL. Dicer1, an independent prognostic factor for predicting shortened survival of patients with PGI-DLBCL, can be used as a biomarker to guide the prognosis.
authors.affiliation: Department of Hematology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, 300060, People's Republic of China.
authors.forename: Haifeng
authors.initials: H
authors.lastname: Zhao
authors.forename: Le
authors.initials: L
authors.lastname: Zhang
authors.forename: Shanqi
authors.initials: S
authors.lastname: Guo
authors.forename: Tian
authors.initials: T
authors.lastname: Yuan
authors.forename: Bing
authors.initials: B
authors.lastname: Xia
authors.forename: FuLian
authors.initials: F
authors.lastname: Qu
authors.forename: Lianyu
authors.initials: L
authors.lastname: Zhang
authors.forename: Yizhuo
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000328:Adult; D000368:Aged; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D060565:Argonaute Proteins / Q000235:genetics; D003520:Cyclophosphamide / Q000627:therapeutic use; D053487:DEAD-box RNA Helicases / Q000235:genetics*; D015536:Down-Regulation; D004317:Doxorubicin / Q000627:therapeutic use; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D006801:Humans; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D011241:Prednisone / Q000627:therapeutic use; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D016601:RNA-Binding Proteins / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D012189:Retrospective Studies; D043244:Ribonuclease III / Q000235:genetics*; D000069283:Rituximab; D015996:Survival Rate; D014750:Vincristine / Q000627:therapeutic use
chemical_list: C466422:AGO2 protein, human; D058846:Antibodies, Monoclonal, Murine-Derived; D060565:Argonaute Proteins; C474043:DGCR8 protein, human; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D000069283:Rituximab; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; C408087:DICER1 protein, human; C517918:DROSHA protein, human; D043244:Ribonuclease III; D053487:DEAD-box RNA Helicases; D011241:Prednisone