Chin-Mu Hsu: Division of Hematology and Oncology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung 807377, Taiwan, R.O.C.
Shih-Yu Kao: Cancer Center, Kaohsiung Medical University Hospital, Kaohsiung 807377, Taiwan, R.O.C.
Chia-Hung Yen: Center for Cancer Research, Kaohsiung Medical University, Kaohsiung 807378, Taiwan, R.O.C.
Chi-En Hsiao: Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA.
Shih-Feng Cho: Division of Hematology and Oncology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung 807377, Taiwan, R.O.C.
Hui-Ching Wang: Division of Hematology and Oncology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung 807377, Taiwan, R.O.C.
Tsung-Jang Yeh: Division of Hematology and Oncology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung 807377, Taiwan, R.O.C.
Jeng-Shiun Du: Division of Hematology and Oncology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung 807377, Taiwan, R.O.C.
Min-Hong Wang: Division of Hematology and Oncology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung 807377, Taiwan, R.O.C.
Tzu-Yu Hsieh: Division of Hematology and Oncology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung 807377, Taiwan, R.O.C.
Samuel Yien Hsiao: Center for Computational and Integrative Biology, University of Rutgers-Camden, Camden, NJ 08102, USA.
Yuhsin Tsai: Graduate Institute of Chinese Medicine, School of Chinese Medicine, China Medical University, Taichung 404328, Taiwan, R.O.C.
Li-Chuan Hung: Department of Long-Term Care and Health Management, Cheng Shiu University, Kaohsiung 833301, Taiwan, R.O.C.
Yi-Chang Liu: Division of Hematology and Oncology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung 807377, Taiwan, R.O.C.
Kung-Chao Chang: Department of Pathology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 701401, Taiwan, R.O.C.
Hui-Hua Hsiao: Division of Hematology and Oncology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung 807377, Taiwan, R.O.C.
Diffuse large B-cell lymphoma (DLBCL) is an aggressive B-cell lymphoma characterized by distinct subtypes and heterogeneous treatment outcomes. Oxidative stress and the dysregulation of related regulatory genes are prevalent in DLBCL, prompting an investigation into the nuclear factor erythroid 2-related factor 2 (Nrf2)-kelch-like ECH-associated protein 1 (Keap1) signaling pathway and associated genes. The present study assessed pathological specimens and clinical data from 43 newly diagnosed patients with DLBCL, comparing the associations and correlations between the expression of Nrf2, Keap1, microtubule-associated protein 1 light chain 3β (LC3B) and nitrotyrosine and the activated B-cell (ABC) and germinal center B-cell (GCB) subtypes of DLBCL using immunohistochemistry and digital image analysis software. Nuclear Nrf2 activation was observed in 33.3% of patients with DLBCL ABC, demonstrating a higher prevalence of hepatitis B surface antigen positivity, calcium ions and significant body weight loss (P<0.05). Total Nrf2 expression was associated with the DLBCL GCB subtype and inversely correlated with Keap1 expression in the DLBCL ABC subtype. Furthermore, a positive correlation was demonstrated between Nrf2 and LC3, indicating that total Nrf2 is inhibited by Keap1 and regulates LC3 expression. The ABC subtype was also associated with lower white blood cell counts and more frequent chemotherapy courses than the GCB subtype. These findings suggest that nuclear Nrf2 could be a biomarker for DLBCL clinical diagnosis.
