title: Reduced or absent cyclin H expression is an independent prognostic marker for poor outcome in diffuse large B-cell lymphoma.
abstract: Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoid malignancy in adults, accounting for nearly 40% of all non-Hodgkin's lymphomas. As cell proliferation is essential for tumor growth, analysis of the cell cycle might give additional information on tumor progression. Although markers distinctive for cell-cycle regulation in DLBCL have been addressed, less attention has been paid to cyclin H in DLBCL with respect to its prognostic and potential therapeutic implications. Cyclin H occurs as a component of the cyclin H/Cdk 7/Mat 1 complex. Cyclin H is also a substrate of protein kinase 2, a ubiquitously expressed serine/threonine protein kinase required for cell viability and cell-cycle progression. We evaluated the expression of cyclin H by immunohistochemistry in 301 DLBCLs in a tissue microarray format. Validation was done by performing quantitative real-time polymerase chain reaction and Western blotting experiments for cyclin H. We studied the relationship between cyclin H expression in comparison to other cyclins (A, B1, D1, D3, and E) and the proliferation marker Ki-67. Reduced or absent cyclin H expression was seen in 14.5% of the DLBCL cases. Interestingly, reduced or absent cyclin H expression was correlated with lower expression of proliferation marker Ki-67 (P < .0001), cyclin B1 (P = .0001), cyclin D3 (P = .0007), and cyclin E (P < .0001). Reduced or absent cyclin H expression was significantly associated with poor overall survival, in both the univariate (P = .0286) and multivariate analysis with International Prognostic Index (P = .0180). Our study demonstrates the independent prognostic value of cyclin H expression in DLBCL and proposes its use as a prognostic marker.
authors.affiliation: Human Cancer Genomics Research Centre, King Fahad National Center for Children's Cancer and Research, King Faisal Specialist Hospital and Research Centre, Riyadh 11211, Saudi Arabia.
authors.forename: Prashant
authors.initials: P
authors.lastname: Bavi
authors.forename: Jehad
authors.initials: J
authors.lastname: Abubaker
authors.forename: Azhar
authors.initials: A
authors.lastname: Hussain
authors.forename: Meher
authors.initials: M
authors.lastname: Sultana
authors.forename: Fouad
authors.initials: F
authors.lastname: Al-Dayel
authors.forename: Shahab
authors.initials: S
authors.lastname: Uddin
authors.forename: Khawla S
authors.initials: KS
authors.lastname: Al-Kuraya
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D056748:Cyclin H; D016213:Cyclins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D016403:Lymphoma, Large B-Cell, Diffuse / Q000378:metabolism* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D012333:RNA, Messenger / Q000378:metabolism; D012334:RNA, Neoplasm / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012529:Saudi Arabia / Q000453:epidemiology; D015996:Survival Rate; D046888:Tissue Array Analysis
chemical_list: D014408:Biomarkers, Tumor; C534751:CCNH protein, human; D056748:Cyclin H; D016213:Cyclins; D012333:RNA, Messenger; D012334:RNA, Neoplasm