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MYC-targeted genes predict distant recurrence in patients with ocular adnexal extranodal marginal zone lymphoma

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Abstract

Ocular adnexal extranodal marginal zone lymphoma (OA-EMZL) is the most frequent subtype of ocular adnexal lymphoma, with a high propensity for recurrence. Distant recurrence (DR) as an essential prognostic event has unique clinical risk factors, but whether distinct molecular features exist remains poorly understood. Here, we identified potential biomarkers using proteomic analysis of 27 OA-EMZL samples. The MYC-targeted genes PCNA, MCM6, and MCM4 were identified as candidates. MYC-targeted genes were further identified as the most significantly activated gene set in patients with DR. The candidate genes were verified in samples from 11 patients with DR and 33 matched controls using immunohistochemistry. The 3-year and 5-year AUC values of MCM6 (0.699 and 0.757) were higher than those of Ki-67 (0.532 and 0.592). High expressions of MCM6 and MCM4 were significantly associated with shorter distant recurrence–free survival (Log-rank p = 0.017, Log-rank p = 0.0053). Multivariate Cox regression identified MCM6 expression as an independent risk factor for DR (HR, 6.86; 95% CI, 1.32–35.79; P = 0.02). Knockdown of c-Myc in B cells resulted in decreased MCM6 and MCM4 expression and reduced proliferative capacity. Our results suggest that activation of the MYC-targeted gene is a distinct molecular feature of DR in OA-EMZL. MYC-targeted gene, MCM6, is a promising pathological biomarker for DR.

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Data availability

The data used to support the findings of this study are available from the corresponding author upon request.

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Funding

This work was supported by Innovative Research Team of High-Level Local Universities in Shanghai (SHSMU-ZDCX20210902), The Science and Technology Commission of Shanghai (20DZ2270800, 19JC1410200), and the Project of Biobank of Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine (YBKA201907; YBKA202208).

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Author notes

  1. Tianyu Zhu, Jiahao Shi, and **aowen Zhou contributed equally to this article.

Authors and Affiliations

  1. Department of Ophthalmology, Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, People’s Republic of China

    Tianyu Zhu, Jiahao Shi, **aowen Zhou, Cen Qiu, Ruobing Jia, Shiyun Huang, Renbing Jia, Yefei Wang, **n Song & Yixiong Zhou

  2. Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, People’s Republic of China

    Tianyu Zhu, Jiahao Shi, **aowen Zhou, Ruobing Jia, Shiyun Huang, Renbing Jia, Yefei Wang, **n Song & Yixiong Zhou

  3. Department of Pathology, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China

    Cen Qiu

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Contributions

Conceptualization: Yixiong Zhou. Methodology: Tianyu Zhu, Jiahao Shi. Formal analysis and investigation: Tianyu Zhu, Jiahao Shi, **aowen Zhou. Writing—original draft preparation: Tianyu Zhu. Writing—review and editing: Tianyu Zhu, Jiahao Shi, Yixiong Zhou. Funding acquisition: Renbing Jia. Resources: Yefei Wang, **n Song, Yixiong Zhou. Supervision: Yefei Wang, **n Song, Yixiong Zhou.

Corresponding authors

Correspondence to Yefei Wang, **n Song or Yixiong Zhou.

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Ethics approval and consent to participate

The research followed the tenets of the Declaration of Helsinki. The collection of the clinical and pathological information was approved by the institutional review board of Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine (approval No. SH9H-2019T185-2).

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Supplementary Information

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Supplementary file1 (PDF 7814 KB)

277_2023_5203_MOESM2_ESM.pdf

Supplementary file2. (A) Time dependent ROC curves of PCNA on DRFS, LRFS and RFS.(B) Kaplan-Meier survival curves for LRFS and RFS by Ki-67, MCM6, and MCM4 expression (cut-off: median H-score).(C) DRFS and LRFS in patients with OA-EMZL and high or low expression of Ki-67, MCM6 and MCM4 (cut-off: AUC value). (PDF 659 KB)

277_2023_5203_MOESM3_ESM.pdf

Supplementary file3. (A), (B): The distribution of propensity scores of distant recurrence (treated) and non-distant recurrence (control) before and after matching clinical characteristics. (PDF 438 KB)

Supplementary file4 (PDF 20 KB)

Supplementary file5 (PDF 12 KB)

Supplementary file6 (PDF 58 KB)

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Zhu, T., Shi, J., Zhou, X. et al. MYC-targeted genes predict distant recurrence in patients with ocular adnexal extranodal marginal zone lymphoma. Ann Hematol 102, 2413–2423 (2023). https://doi.org/10.1007/s00277-023-05203-8

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  • DOI: https://doi.org/10.1007/s00277-023-05203-8

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