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Expression profiling reveals coordinated dysregulation of autophagy‑associated proteins in marginal zone lymphoma and therapeutic implications

  • Authors:
    • Jingshu Ruan
    • Xin Zhou
    • Ai Li
    • Ningning Shan
  • View Affiliations / Copyright

    Affiliations: Department of Hematology, The Second Hospital of Shandong University, Jinan, Shandong 250033, P.R. China, Department of Hematology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong 250021, P.R. China
    Copyright: © Ruan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 68
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    Published online on: December 3, 2025
       https://doi.org/10.3892/ol.2025.15421
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Abstract

Dysregulated autophagy and its therapeutic targeting have emerged as focal points in oncology research; however, specific studies investigating autophagy in marginal zone lymphoma (MZL) pathogenesis remain limited. The present study comprehensively characterized the expression profiles of key autophagy‑related proteins in MZL, providing novel mechanistic insights and an experimental rationale for therapeutic intervention. Immunohistochemical analysis assessed the expression of Beclin‑1, light chain (LC)3, sequestosome (SQSTM)1/p62 and Bcl‑2 in formalin‑fixed paraffin‑embedded tissues from 16 patients with MZL compared with 16 reactive lymphoid hyperplasia (RLH) controls. MZL specimens exhibited significant autophagy pathway dysregulation, characterized by ~35‑40% decreased expression of Beclin‑1 and LC3 and 30‑45% increased expression of SQSTM1/p62 and Bcl‑2 compared with RLH tissues (P<0.05 for all proteins analyzed). The present findings delineate a distinct profile of autophagy dysfunction in MZL, highlighting aberrant Beclin‑1, LC3, SQSTM1/p62 and Bcl‑2 expression as potential disease biomarkers and therapeutic targets. This study provides a critical basis for elucidating the molecular mechanisms underlying MZL pathogenesis and underscores the therapeutic potential of modulating autophagy‑related pathways.
View Figures

Figure 1

Beclin-1 protein expression in MZL
and RLH tissues. (A) Representative immunohistochemical staining
for Beclin-1 in MZL and RLH samples. (B) Statistical comparison of
Beclin-1 expression between MZL and RLH tissues (analyzed by
unpaired t-test. *P<0.05). MZL, marginal zone lymphoma; RLH,
reactive lymphocyte hyperplasia; AOD, average optical density.

Figure 2

LC3 expression is significantly
decreased in MZL tissues. (A) Representative immunohistochemical
images showing LC3 staining in RLH and MZL samples (left panel:
Magnification, ×20; overview. Right panel: Magnification, ×40;
detailed view). (B) Statistical analysis demonstrating significant
differences in LC3 expression between MZL and RLH groups (unpaired
t-test, ****P<0.0001). LC3, light chain 3; MZL, marginal zone
lymphoma; RLH, reactive lymphocyte hyperplasia; AOD, average
optical density.

Figure 3

Elevated expression of p62 in MZL
tissues compared to RLH controls. (A) Representative images of p62
immunohistochemical staining in MZL and RLH samples. (B)
Statistical comparison of p62 expression between MZL and RLH groups
(unpaired t-test, **P<0.01). MZL, marginal zone lymphoma; RLH,
reactive lymphocyte hyperplasia; AOD, average optical density.

Figure 4

Bcl-2 expression is significantly
increased in MZL tissues. (A) Representative IHC staining of Bcl-2
in MZL and RLH samples (left panel: Magnification, ×20; overview.
Right panel: Magnification, ×40; detailed view). (B) Statistical
comparison of Bcl-2 expression between MZL and RLH groups (unpaired
t-test, ****P<0.0001). MZL, marginal zone lymphoma; RLH,
reactive lymphocyte hyperplasia; AOD, average optical density.
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Copy and paste a formatted citation
Spandidos Publications style
Ruan J, Zhou X, Li A and Shan N: Expression profiling reveals coordinated dysregulation of autophagy‑associated proteins in marginal zone lymphoma and therapeutic implications. Oncol Lett 31: 68, 2026.
APA
Ruan, J., Zhou, X., Li, A., & Shan, N. (2026). Expression profiling reveals coordinated dysregulation of autophagy‑associated proteins in marginal zone lymphoma and therapeutic implications. Oncology Letters, 31, 68. https://doi.org/10.3892/ol.2025.15421
MLA
Ruan, J., Zhou, X., Li, A., Shan, N."Expression profiling reveals coordinated dysregulation of autophagy‑associated proteins in marginal zone lymphoma and therapeutic implications". Oncology Letters 31.2 (2026): 68.
Chicago
Ruan, J., Zhou, X., Li, A., Shan, N."Expression profiling reveals coordinated dysregulation of autophagy‑associated proteins in marginal zone lymphoma and therapeutic implications". Oncology Letters 31, no. 2 (2026): 68. https://doi.org/10.3892/ol.2025.15421
Copy and paste a formatted citation
x
Spandidos Publications style
Ruan J, Zhou X, Li A and Shan N: Expression profiling reveals coordinated dysregulation of autophagy‑associated proteins in marginal zone lymphoma and therapeutic implications. Oncol Lett 31: 68, 2026.
APA
Ruan, J., Zhou, X., Li, A., & Shan, N. (2026). Expression profiling reveals coordinated dysregulation of autophagy‑associated proteins in marginal zone lymphoma and therapeutic implications. Oncology Letters, 31, 68. https://doi.org/10.3892/ol.2025.15421
MLA
Ruan, J., Zhou, X., Li, A., Shan, N."Expression profiling reveals coordinated dysregulation of autophagy‑associated proteins in marginal zone lymphoma and therapeutic implications". Oncology Letters 31.2 (2026): 68.
Chicago
Ruan, J., Zhou, X., Li, A., Shan, N."Expression profiling reveals coordinated dysregulation of autophagy‑associated proteins in marginal zone lymphoma and therapeutic implications". Oncology Letters 31, no. 2 (2026): 68. https://doi.org/10.3892/ol.2025.15421
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