High WEE1 expression is independently linked to poor survival in multiple myeloma Journal Article

   


Authors: Simhal, A. K.; Firestone, R. S.; Oh, J. H.; Avutu, V.; Norton, L.; Hultcrantz, M.; Usmani, S. Z.; Maclachlan, K. H.; Deasy, J. O.
Article Title: High WEE1 expression is independently linked to poor survival in multiple myeloma
Abstract: Current prognostic scores in multiple myeloma (MM) currently rely on disease burden and a limited set of genomic alterations. Some studies have suggested gene expression panels may predict clinical outcomes, but none are presently utilized in clinical practice. The tyrosine kinase WEE1 is a critical cell cycle regulator during the S-phase and G2M checkpoint. Abnormal WEE1 expression has been implicated in multiple cancers including breast, ovarian, and gastric cancers, but its prognostic signal in MM has not been thoroughly reported. We, therefore, analyzed the MMRF CoMMpass dataset (N = 659) and identified a high-risk group (top tertile) and a low-risk group (bottom tertile) based on WEE1 expression sorted in descending order. PFS was significantly different (p < 1e-9) between the groups, which was validated in two independent microarray gene expression profiling (GEP) datasets from the Total Therapy 2 (N = 341) and 3 (N = 214) trials. Our results show that WEE1 expression is prognostic independent of known biomarkers, differentiates outcomes associated with known markers, is upregulated independently of its interacting neighbors, and is associated with dysregulated P53 pathways. This suggests that WEE1 expression levels may have clinical utility in prognosticating outcomes in newly diagnosed MM and may support the application of WEE1 inhibitors to MM preclinical models. Determining the causes of abnormal WEE1 expression may uncover novel therapeutic pathways. © The Author(s) 2025.
Keywords: adult; controlled study; human tissue; middle aged; survival analysis; unclassified drug; major clinical study; genetics; mortality; cell cycle protein; metabolism; cell cycle proteins; cell cycle; progression free survival; bortezomib; multiple myeloma; gene expression profiling; cell differentiation; pathology; protein tyrosine kinase; tumor marker; risk factor; gene expression regulation; gene expression regulation, neoplastic; mitosis spindle; protein-tyrosine kinases; high risk population; carfilzomib; protein wee1; wee1 protein, human; clinical outcome; independent variable; low risk population; g2 phase cell cycle checkpoint; humans; prognosis; human; male; female; article; rna sequencing; prognostic assessment; differential gene expression; biomarkers, tumor; prediction error
Journal Title: Blood Cancer Journal
Volume: 15
ISSN: 2044-5385
Publisher: Nature Publishing Group  
Date Published: 2025-02-20
Start Page: 22
Language: English
DOI: 10.1038/s41408-025-01230-y
PUBMED: 39979284
PROVIDER: scopus
PMCID: PMC11842801
DOI/URL:

https://www.scopus.com/inward/record.uri?eid=2-s2.0-85218632617&doi=10.1038%2fs41408-025-01230-y&partnerID=40&md5=c4dfddfcfadc1fea2dd1c2cbee2c0330
Notes: Article -- MSK Cancer Center Support Grant (P30 CA008748) acknowledged in PubMed and PDF -- MSK corresponding author is Anish Shimhal -- Source: Scopus
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MSK Authors
  1. Larry Norton
    760 Norton
  2. Jung Hun Oh
    188 Oh
  3. Joseph Owen Deasy
    527 Deasy
  4. Malin Lisa Hultcrantz
    268 Hultcrantz
  5. Kylee Maclachlan
    155 Maclachlan
  6. Viswatej Avutu
    35 Avutu
  7. Saad Zafar Usmani
    327 Usmani
  8. Anish Kumar Simhal
    15 Simhal
  9. Ross Firestone
    40 Firestone
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