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Clinicopathologic significance of MYD88 L265P mutation and expression of TLR4 and P-STAT3 in primary central nervous system diffuse large B-cell lymphomas

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Abstract

Patients with primary central nervous system lymphoma (PCNSL) have a prognosis poorer than that of systemic lymphoma patients. In patients with this condition, TLR4/STAT3 pathway alterations and the MYD88 L265P mutation may be viable targets for therapeutic intervention. The present study was, therefore, designed to identify clinicopathologic correlates of MYD88 mutations and TLR4/STAT3 pathway alterations in PCNSL. We detected TLR4 and p-STAT3 in 41.5% (22/53) and 43.4% (23/53) of PCNSL patients, respectively, while 60.4% of these patients (32/53) were found to harbor the MYD88 L265P mutation. TLR4 expression was found to be significantly associated with the presence of multiple brain lesions, while p-STAT3 expression was significantly linked to advanced age, the presence of multiple brain lesions, non-GCB histological findings, and non-CR status. The presence of the MYD88 L265P mutation was significantly linked to advanced age, the presence of multiple brain lesions, and DLBCL molecular subtype. Multivariate analyses additionally confirmed that elevated TLR4 and p-STAT3 expression levels are associated with a poorer PCNSL patient prognosis. Based on these findings, we hypothesize that signaling through the TLR4/MYD88/STAT3 pathway plays a key role in the pathogenesis of PCNSL.

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Acknowledgements

This study was supported by Heilongjiang Postdoctoral Financial Assistance, NO. LBH-Z18169, by the China Postdoctoral Science Foundation, NO. 2019M651306, and by National Natural Science Foundation of China, NO. 81903063

Funding

This study was supported by Heilongjiang Postdoctoral Financial Assistance, NO. LBH-Z18169, by the China Postdoctoral Science Foundation, NO. 2019M651306, and by National Natural Science Foundation of China, NO. 81903063.

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Author notes

  1. Dabei Tang and Wenjia Su made the same contribution to the paper, and should be recognized as co-first authors.

Authors and Affiliations

  1. Department of Medical Oncology, Harbin Medical University Cancer Hospital, Haping Road No. 150, Harbin, Heilongjiang, 150081, People’s Republic of China

    Dabei Tang, Xiaowei Wang, Zhong Chu, Lei Zhang & Qingyuan Zhang

  2. Department of Medical Oncology, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, 150001, People’s Republic of China

    Wenjia Su & Jin Zhou

Authors
  1. Dabei Tang
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  2. Wenjia Su
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  3. Xiaowei Wang
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  4. Zhong Chu
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  5. Lei Zhang
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  6. Jin Zhou
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  7. Qingyuan Zhang
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Contributions

All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by DT, WS, XW, ZC, and LZ. The first draft of the manuscript was written by DT, WZ, JZ, and QZ. All authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Jin Zhou or Qingyuan Zhang.

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The authors declare that there are no conflicts of interest.

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The study was approved by the ethics committee of the Harbin medical university cancer hospital and the First Affiliated Hospital of Harbin medical university.

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Tang, D., Su, W., Wang, X. et al. Clinicopathologic significance of MYD88 L265P mutation and expression of TLR4 and P-STAT3 in primary central nervous system diffuse large B-cell lymphomas. Brain Tumor Pathol 38, 50–58 (2021). https://doi.org/10.1007/s10014-020-00386-8

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