Cyclin D1-positive expression associated with prognostic significance and clinicopathological characteristics by paving the way for proliferation in diffuse large B-cell lymphomas Provisionally Accepted
Xiping Liang1, 2
Renzhi Hu2
Chaoyu Wang2
Qiying Li2
Xiaoju Li2
Bingling Guo2
Chunyan Xiao2
Yao Liu2*
- 1Department of Hematology-Oncology，Chongqing University Cancer Hospital, Chongqing, China, China
- 2Cancer Hospital, Chongqing University, China
Introduction: Cyclin D1 protein expression has rarely been reported in patients with diffuse large B-cell lymphoma (DLBCL), and the clinical implications of cyclin D1 in Asia remain unclear. Methods: In this study, a total of 815 patients diagnosed with DLBCL were reviewed. The authors conducted clinical, immunohistochemical, and genetic analyses, with a specific focus on cyclin D1. Results: Among the DLBCL patients, 16 individuals (2.61%) exhibited cyclin D1 expression without CCND1 gene rearrangements. Cyclin D1-positive DLBCLs were observed in patients with a median age of 58.88 ± 4.07 years, with 93.75% of them classified as stage IV. A comparison was made between DLBCL patients with and without cyclin D1 expression in terms of clinical, immunohistochemical, and genetic features. Cyclin D1-positive DLBCLs were associated with elevated LDH levels, higher IPI scores, advanced stage, increased Ki-67 proliferation, MYC expression and inferior survival outcomes. All samples exhibited BRD9 and NOTCH2NL gene mutations, while gene alterations in the PI3K/AKT signaling pathways were evident in cyclin D1-positive DLBCLs. More pronounced variation in the MTOR gene was observed between cyclin D1-positive and negative patients. Notably, DLBCL patients with cyclin D1 expression frequently exhibited CDKN2A and CDKN2B gene deletions, known to regulate the cell cycle transition from G1 to S phase in tumors. Conclusion: Cyclin D1-positive DLBCL patients exhibited aggressive clinical behavior and inferior survival outcomes. NGS studies revealed potential associations with abnormal cell cycle transition and the AKT pathway. These findings may suggest the existence of a distinct subset of DLBCL. key words：Cyclin D1, DLBCL, Abnormal cell cycle transition, AKT pathway, Outcomes
Keywords: Cyclin D1, DLBCL, Abnormal cell cycle transition, AKT pathway, outcomes
Received: 24 Nov 2023;
Accepted: 13 May 2024.
Copyright: © 2024 Liang, Hu, Wang, Li, Li, Guo, Xiao and Liu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Prof. Yao Liu, Cancer Hospital, Chongqing University, Chongqing, 400030, Anhui, China